Madsen Lab

Curvature-Dependent Trafficking of Transmembrane Proteins

STEPPING STONE:  My passion to understand the interplay between membrane proteins and lipid membranes dates back ot my entry in science. Ignited in my bachelor studies, which dealt with the regulation of ion channels by amphiphiles (Søgaard et al, 2006) and sparked in a collaboration with Dimitrios Stamou, UCPH focused on basic understanding of protein-lipid interactions resulting in two seminal papers (Bhatia et al, EMBO, 2009), (Hatzakis et al, NCB, 2009), both cited 300+ times. My group has focused on membrane trafficking processes and their regulation by scaffold proteins, using high-throughput methods (e.g. Thorsen*, Madsen* et al, PNAS, 2010) and advanced live microscopy (e.g. Rathje et al, PNAS, 2013). In parallel work with direct implications for the proposed project, we have investigated protein motifs that sense and shape membrane curvature during cellular trafficking processes. This work has involved the development of isolated sheets of cell membranes for the study of binding of peripheral membrane proteins to membranes (Skamris et al, Scientific Reports, 2019) and membrane-embedded receptors (Erlendsson et al, eLife, 2018), (VB Kasaragod et al, Neuron, 2019). Moreover, we have provided the first direct demonstration of membrane curvature sensing within cells using super-resolution microscopy (Herlo et al, Cell Reports, 2019). Finally, we reviewed the dynamic association of peripheral membrane proteins with membrane curvature (Madsen et al, FEBS Letters, 2010; Erlendsson et al, Membranes, 2015 and Madsen et al, Membranes, 2017).

ONGOING WORK : In 2025, we published a fundamentally novel trafficking mechanism that is complementary to traditional adaptor-based trafficking mechanisms in the context of GPCRs (Schmidt, Herlo et al, Science Advances 2025), which posits that Helix 8 in GPCRs drives constitutive endocytosis by association with high membrane curvature. We have subsequently identified similar curvature sensitive trafficking motifs in ~ 40% of all transmembrane proteins across all major families in a proteome screen (Rombach et al. BioRxiv 2025), and this data has been made publicly available through the MEMRIDR app. This screen pointed to particular relevance for this mechanism in the context of proteins localizing to synaptic vesicles, which we are currently investigating together with Volker Haucke FMR, Berlin. Future work will address the role of this novel trafficking mechanism in relation to protein turnover and stability, localisation of glycosyl transferase in the secretory pathway and transcriptional changes e.g. in cancer and oligodendrocytes transitions. Finally, we will probe the potential for using our map of highly internalizing membrane proteins as Trojan horses for anti-cancer drug conjugates. This work is funded by the Danish Research Council.

Understanding the role of PICK1 in disease

STEPPING STONE:  I established my scientific core by studying protein-protein interactions with a focus on PDZ interactions and the function of the synaptic PDZ domain protein PICK1. In parallel, it became clear that PICK1 might be an attractive molecular target in drug addiction and pain. Using my expertise on PICK1 and PDZ interactions, we developed and patented the first small molecule inhibitors for this type of proteins together with Neurosearch A/S (Thorsen*, Madsen* et al PNAS 2010). As an independent researcher, I subsequently solved the PICK1 structure (Karlsen et al, Structure, 2015) and developed a novel quantitative method for assessing binding of scaffold proteins to membrane proteins in their native membrane environment (Erlendsson...Madsen, eLife, 2019). Together, these efforts have enabled the rational design and patenting of bivalent, high-affinity inhibitors to potently target PICK1 in pain and addiction. Inhibition of PICK1 is unique in the sense that it selectively targets the hyperexcitable transmission characterizing these pathologies without affecting overall transmission (Christensen...Madsen, EMBO Mol. Med., 2020; and Jensen et al, Frontiers in Cell. Neu. 2022). In concordance with the involvement of PICK1 in addiction, we have demonstrated that iv administration of the PICK1 inhibitor reduces cocaine craving in a rat model of reinstatement (Turner et al, Neuropharm, 2020). We have refined the development of a small dimeric peptide and virally expressed inhibitors of PICK1 and their effect in mouse models of inflammatory and neuropathic pain (Jensen et al, JCI Insight, 2024 and Noes-Holt et al, BioRxiv, 2023 – in revision for Cell Reports Medicine). Both Manuscripts have led to IDFs and subsequent patent applications (P5521EP00 and P5457EP00) and the establishment of the spin-out company Zyneyro.

In a parallel effort, we discovered a regulatory role of PICK1 in maturation of dense core vesicles in the pituitary and pancreatic beta-cells (Holst*, Madsen* et al, Plos Bio, 2013). This has led us to the subsequent identification of a functional role of PICK1 in the storage/release machinery in neurons and chromaffin cells. We followed these findings up describing the molecular mechanism by which PICK1 is recruited to lipid membranes of high curvature, which was the first demonstration of this cellular localization mechanism in living cells (Herlo…Madsen, Cell Reports, 2018) and showing the translational relevance of these findings by describing 4 coding variants in PICK1 identified in patients with type 2 diabetes that modulate insulin processing in beta-cells (Andersen et al, JCI, 2022). Work performed in collaboration with Christoffer Clemmensen has demonstrated the s.c. administration of the PICK1 inhibitor provides weight reduction in Diet Induced Obese mice (Science Adv. 2024).

ONGOING WORK: In work funded by an Ascending investigator grant from the Lundbeck foundation and an ascending investigator grant within Endocrinology and Metabolism from the NOVO Nordisk Foundation, we are combining omics approaches with intravital microscopy to characterize and understand the molecular mechanism underlying the potent effect of inhibiting the target proteins PICK1 in peripheral neurons in neuropathic pain models and obesity. Furthermore, we use whole-brain cFOS light sheet microscopy and a novel analytical tool together with neurotransmitter biosensors and systems neuroscience approaches to untangle the interoceptive (Brain-body communication) aspects following from inhibition of PICK1 in these conditions. 

Herlo R., Schmidt J. H., Rombach J., Larsen A. H., Stoklund M., Perslev M., Nielsen T. T. E., Andersen K. A., Herenbrink C. K., Lycas M. D., Ejdrup A. L., Christensen N. R., Christensen J. P., Salman M., Herborg F., Gether U., Hauser A. S., Bassereau P., Perrais D., #Madsen K. L. ‘Membrane curvature association of amphipathic helix 8 drives constitutive GPCR endocytosis’ Science Advances, 2025

Jensen, K. L.; Chistensen, N. R.; Noes-Holt, G.; Kanneworff, I. B.; Sivertsen, L.; Baro, R. C.; Jiménez-Fernández, L.; Goddard, C. M.; Hopkins C.; Thomsen, C. D.; Soltan A. B. I.; del Castillo, M. D.; Jager, S. E.; Tidemand F. G.; Arleth, L.;  Heegaard, A.; Sørensen, A. T. #Madsen, K. L. ‘mPD5, an efficacious PICK1 inhibitor for treating chronic pain’. JCI insight, 2024

Fadahunsi, N.; Petersen, J.; Metz, S.; Jakobsen, A.; Mathiesen, C. V.;  Buch-Rasmussen, A.S.; Kurgan, N.K.; Larsen, J. K.; Andersen, R. C.; Topilko, T.; Svendsen, C.; Apuschkin, M.; Skovbjerg, G.; Schmidt, J. H.; Houser, G.A.;Jager, S. E.; Bach, A.; Deshmukh, A.; Kilpeläinen, T. O.; Strømgaard, K.; Madsen, K. L.; Clemmensen C. ‘Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment’ Science Advances, 2024

Ejdrup AL, Lycas MD, Lorenzen N, Konomi A, Herborg F, Madsen KL, Gether U. ‘A density-based enrichment measure for assessing colocalization in single-molecule localization microscopy data.’ Nature Commun. 2022

R. Andersen , M.D. Lycas , J. H. Schmidt , N. R. Christensen , V. K. Lund , J. Rombach , M. Stoklund , D. S. Stapleton , G. Noes-Holt, M. P. Keller , A. M. Jansen , R. Herlo , O. Kjærulff , B. Holst , A. D. Attie , U. Gether and K. L. Madsen ‘Coding variants identified in diabetic patients alter PICK1 BAR domain function in insulin granule biogenesis’ Journal of Clinical Investigations, 2022

Christensen NR*, De Luca M*, Lever MB, Richner M, Hansen AB, Jensen KL, Rathje M, Noes-Holt G, Jensen DB, Erlendsson S, Bartling CRO, Ammendrup-Johnsen I, Pedersen SE, Schönauer M, Nissen KB, Midtgaard SR, Teilum K, Arleth L, Sørensen AT, Bach A, Strømgaard K, Meehan CF, Vægter CB, Gether U, Madsen KL 'A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain' EMBO Molecular Medicine, 2020

Erlendsson S*, Thorsen TS*, Vauquelin G, Ammendrup-Johnsen I, Wirth V, Martinez KL, Teilum K, Gether U, Madsen KL. ‘Mechanisms of PDZ domain scaffold assembly illuminated by use of supported cell membrane sheets.’ Elife. 2019

Lund VK, Madsen KL, Kjaerulff O 'Drosophila Rab2 controls endosome–lysosome fusion and LAMP delivery to the endolysosomal pathway Autophagy 2018

Herlo R, Lund VK, Lycas MD, Jansen AM, Khelashvili G, Andersen RC, Bhatia V, Pedersen TS, Albornoz PBC, Johner N, Ammendrup-Johnsen I, Christensen NR, Erlendsson S, Stoklund M, Larsen JB, Weinstein H, Kjærulff O, Stamou D, Gether U, Madsen KL.'An amphipathic helix directs cellular membrane curvature sensing and function of the BAR domain protein PICK1' Cell Reports 2018

Holst B*, Madsen KL*, Jansen AM, Jin C, Rickhag M, Lund VK, Jensen M, Bhatia V, Sørensen G, Madsen AN, Xue Z, Møller SK, Woldbye D, Qvortrup K, Huganir R, Stamou D, Kjærulff O, Gether U. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. PLoS Biol. 2013

Madsen KL ‘PICK1 inhibitors for treatment of overweight and obesity’ P89111DK, Filed January, 2024, Priority Application

Madsen KL ‘PICK1 inhibitors with improved linker and tail’ P89112DK, Filed January, 2024, Priority Application

Madsen KL ‘Peptide ligand with lipidated linker for treatment of overweight and obesity’ P89113DK, Filed January, 2024, Priority Application

Madsen KL ‘PICK1 inhibitors with restructured binding motif’ P89114DK, Filed January, 2024, Priority Application

Madsen KL, Christensen NR, Gether U 'A fatty acid bivalent inhibitor targeting PICK1' P5521EP00, Filed March, 2020

Sørensen AT, Madsen KL, Christensen NR, Strømgaard K 'Viral multimeric peptide constructs for targeting PDZ domains' P5457EP00, Filed March, 2020

Madsen KL, Strømgaard K, Bach A, Christensen NR, Gether U 'Inhibitors of PICK1 and uses thereof', P4997EP00, Filed November 2018, Granted in Europe

Sørensen AT, Madsen KL, Christensen NR, Strømgaard K 'Virally expressed inhibitors of PDZ domains, such as PICK1 and uses thereof' P5036EP00, Filed November 2018

Madsen KL, Thorsen TS, Peters D, Dyhring T, Rønn LC, Gether U. PDZ DOMAIN MODULATORS. Danish patent application No. PA 2007 00828 (filed on 8 June 2007) and US provisional application No. 60/942,860 (filed on 8 June 2008) was filed on 3 June 2008 (Application No. PCT/EP2008/056814)

Education

• PhD, Faculty of Health Sciences, University of Copenhagen (UCPH), 2005-08
• M.Sc., Biochemistry, UCPH, 2002-04
• Bachelor, Biochemistry, UCPH, 1998-01
• Bachelor, Geography, UCPH, 1994-97 

Appointments and Positions

• Associate Professor, Dept. of Neuroscience, UCPH (2013–present, 80%)
• In external evaluation for full professor within the UCPH promotion programme for full professor
• Founder, KLMBio & DOLORESTBIO (now Zyneyro), 2021; 20% employed at Zyneyro
• Postdoc, UCPH Programme of Excellence, 2008-10; personal grant from FSS, 2010-13
• PhD scholarship, Faculty of Health Sciences, UCPH, 2004-07
• M.Sc. scholarship, Bioteknologirådet, 2002-04

Company and Industry Activities

• Zyneyro: Licensed IPR for tPD5, mPD5, AAV expressed analogues
• Partnership with Swedish CombiGene (2022–24, €3m) for PICK1 inhibitors in pain
• Received new investment (1 year, €2m) as of March 2025

Publications and Scientific Activities

51 peer reviewed papers (Science Advances, JCI, EMBO Mol Med. Plos Biology, Nat Chem Bio, PNAS, EMBO, JNS, Nature Com, Cell Reports, Elife, Structure, JBC), 8 first, 20 corresponding Author, 2800 citations, H-index 26, 9 Patents/applications.

International Talks since 2017

2025 DANDRITE Symposium, The Adaptive Brain, Aarhus, Denmark

2023 EMBO Conference, Endocytic trafficking and disease, Venice, Italy

2019 EMBO Conference, Endocytic trafficking and disease, Ischia, Italy

2019 Winter Conference on Brain Research (WCBR), Aspen, Colorado, USA

2018 GRC, Endosomes and lysosome, Proctor, USA

2017 EMBO Conference, Endocytic trafficking and signaling, Seerock, Poland

2017 Molecular basis for membrane remodelling and organization, Roscoff, France

Public Communication

• 2022, 2024: Kulturnat ’Test Your Pain Threshold’ workshop
• UCPH press-release, 30/4/2020: New therapy for chronic pain
• Coverage: Verdens Gang (VG), Norway (23/6/2020); Ekstrabladet, Denmark (19/9), major headlines

Grants (since 2018 >40mio dkk)

2025                    Ascending Investigator, Endocrinology and Metabolism, NNF (11.400.000)

2024                    Ascending Investigator, LBF (6.000.000)

2022                    Pioneer Innovators, NNF (1.000.000)

2022                    Research project1, DFF (2.500.000)

2021                    Lundbeck Experiment, Lundbeck Foundation (2.000.000)

2021                    Endocrinology and Metabolism - Nordic, NOVO Nordisk Foundation (1.600.000)

2020                    Bioscience and Basic Biomedicine, NNF (1.600.000)

2020                    Ascending Investigator LBF (5.100.000)

2019                    Lundbeck Experiment, LBF (2.000.000)

2019                    InnoExplorer (1.500.000)

2019                    NOVO Seeds PreSeed (3.500.000)

2018                    Endocrinology and Metabolism - Nordic, (NNF) (1.400.000)

Reviewer task and assessment committees

I review for Nat Struct. & Mol. Bio., Nat. Chem. Bio. Nat. Com., JCI, EMBO, Journal of Cell Bio., ACS Nano, Biochem. J., Biomembranes. Also, I serve as a Review Editor in Membrane Physiology and Membrane Biophysics. I served on several European grant review committees and as opponent on 6 PhD defenses (5 in Denmark and 1 in Sweden) and foreperson on 4 PhD committees.

Positions of trust

• Innovation Ambassador, Department of Neuroscience.
• Hiring committee for Vice Dean for Innovation, 2024
• Department supervisor for UCPH University Pedagogic (UP) (3 mentees).
• Active on the UCPH Mentor Programme (2 mentees)
• Advisory Board for Center for Integrated Microscopy, Chairman
• Advisor Board for Protein Research Infrastructure, Mass Spectrometry

Supervision

I have supervised students since early on in my PhD, 6 bachelor projects, 17 master projects

7 PhDs (co-supervised 6). Currently supervising 2 postdocs and 6 PhD students (3 handing in this year).

• Protein trafficking of transmembrane proteins (by flowcytometry, confocal microscopy, TIRF microscopy of pHluorin)
• Neuronal signaling (by live fluorescence imaging of FRET based biosensors for PKA, PKC etc)
• Nano-structures of receptor-Scaffold complexes and membrane structures (by super resolution microscopy and 'supported cell membrane sheets’)
• Protein-protein interactions (in vitro by fluorescence polarization, SPOT, ex vivo/in vivo by Co-IP and Bio-ID)
• Semi-high throughput screening (by fluorescence polarisation)
• Protein-lipid interactions (by flow cytometry and SPOT)

#Correspondance

Lund V.K., Chirco A., Caliari M., Larsen A.H., Tang K.T., Gether U., Madsen K.L, Wierer M., Kjaerulff O. ‘A Syd and RUFY dynein adaptor complex mediates axonal circulation of dense core vesicles’ Journal of Cell Biology, 2026, Jan 6; 225(3).

Rombach J., Nielsen T.T.E., Schmidt J.H., Agenant J., Larsen A.H., #Madsen K.L. ‘A proteome-wide screen for membrane-interactions in intrinsically disordered regions of transmembrane proteins reveals a role in disease’ bioRxiv 2025.08.15.670465; doi: https://doi.org/10.1101/2025.08.15.670465

Bjørn-Yoshimoto W. E., Ramiro I. B. L., Koch T. L., Engholm E., Yeung H. Y., Sørensen K. K., Goddard C. M., Jensen K. L., Smith N. A., Martin L. F., Smith B. J., Madsen K. L., Jensen K. J., Patwardhan A., Safavi-Hemami H. ‘Venom-inspired somatostatin receptor 4 (SSTR4) agonists as new drug leads for peripheral pain conditions’ Scientific Reports, 2025 Nov 28;15(1):42638.

Herlo R., Schmidt J. H., Rombach J., Larsen A. H., Stoklund M., Perslev M., Nielsen T. T. E., Andersen K. A., Herenbrink C. K., Lycas M. D., Ejdrup A. L., Christensen N. R., Christensen J. P., Salman M., Herborg F., Gether U., Hauser A. S., Bassereau P., Perrais D., #Madsen K. L. ‘Membrane curvature association of amphipathic helix 8 drives constitutive GPCR endocytosis’ Science Advances, 2025, Aug 15;11(33):eadv1499.

Pedersen SE, Konomi-Pilkati A, Hansen NW, Kvist T, Posselt LP, Andreassen TF, Sørensen AT, Perrier JF, #Madsen KL ‘Glutamate receptor-dependent cytosolic acidification in hippocampal neurons involves passive flux of protons from the extracellular space’ bioRxiv 2024.11.17.624027; doi: https://doi.org/10.1101/2024.11.17.624027

Fadahunsi, N.; Petersen, J.; Metz, S.; Jakobsen, A.; Mathiesen, C. V.;  Buch-Rasmussen, A.S.; Kurgan, N.K.; Larsen, J. K.; Andersen, R. C.; Topilko, T.; Svendsen, C.; Apuschkin, M.; Skovbjerg, G.; Schmidt, J. H.; Houser, G.A.;Jager, S. E.; Bach, A.; Deshmukh, A.; Kilpeläinen, T. O.; Strømgaard, K.; Madsen, K. L.; Clemmensen C. ‘Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment’ Science Advances, 2024 Mar;10(9):eadg2636.

Jensen, K. L.; Christensen, N. R.; Noes-Holt, G.; Kanneworff, I. B.; Sivertsen, L.; Baro, R. C.; Jiménez-Fernández, L.; Goddard, C. M.; Hopkins C.; Thomsen, C. D.; Soltan A. B. I.; del Castillo, M. D.; Jager, S. E.; Tidemand F. G.; Arleth, L.;  Heegaard, A.; Sørensen, A. T. #Madsen, K. L. ‘mPD5, an efficacious PICK1 inhibitor for treating chronic pain’. JCI insight, 2024 Sep 17;9(20):e170976.

Noes-Holt G., Jensen K. L., Richner M., Baro R. C., Sivertsen L., Jager S. E., Fernández L. J., Andersen R. C., Lilja J. H., Larsen A. H., Christensen N. R., Tappe-Theodor A., Vægter C. B., Kuner R., Madsen K. L., Sørensen A. T. ‘Recombinant dimeric PDZ protein inhibitors for long-term relief of chronic pain by AAV therapeutics’ bioRxiv 2023. In review with Cell Reports Medicine 03.03.530962; doi: https://doi.org/10.1101/2023.03.03.530962

Jørgensen SH, Ejdrup AL, Lycas MD, Posselt LP, Madsen KL, Tian L, Dreyer JK, Herborg F, Sørensen AT, Gether U. ‘Behavioral encoding across timescales by region-specific dopamine dynamics.’ PNAS. 2023 Feb 14;120(7):e2215230120.

Backe MB, Andersen RC, Jensen M, Jin C, Hundahl C, Dmytriyeva O, Treebak JT, Hansen JB, Gerhart-Hines Z, Madsen KL, Holst B. 'PICK1-Deficient Mice Maintain Their Glucose Tolerance During Diet-Induced Obesity.’ J Endocr Soc. 2023 May 16;7(6):bvad057.

Ejdrup AL, Lycas MD, Lorenzen N, Konomi A, Herborg F, Madsen KL, Gether U. ‘A density-based enrichment measure for assessing colocalization in single-molecule localization microscopy data.’ Nature Commun. 2022. Jul 28;13(1):4388

R. Andersen, M.D. Lycas, J. H. Schmidt, N. R. Christensen, V. K. Lund, J. Rombach, M. Stoklund, D. S. Stapleton, G. Noes-Holt, M. P. Keller, A. M. Jansen, R. Herlo, O. Kjærulff, B. Holst, A. D. Attie , U. Gether and #KL Madsen ‘Coding variants identified in diabetic patients alter PICK1 BAR domain function in insulin granule biogenesis’ Journal of Clinical Investigations, 2022, Mar 1;132(5):e144904.

Christensen NR, Pedersen CP, Sereikaite V, Pedersen JN, Vistrup-Parry M, Sørensen AT, Otzen D, Teilum K, Madsen KL, Strømgaard K. ’Bidirectional protein-protein interactions control liquid-liquid phase separation of PSD-95 and its interaction partners.’ iScience. 2022 Jan 25;25(2):103808.

Jensen K.L., Noes-Holt G, Sørensen A. T., #Madsen K.L.’A Novel Peripheral Action of PICK1 Inhibition in Inflammatory Pain’ Front Cell Neurosci, 2021 15:750902.

Christensen NR*, De Luca M*, Lever MB, Richner M, Hansen AB, Jensen KL, Rathje M, Noes-Holt G, Jensen DB, Erlendsson S, Bartling CRO, Ammendrup-Johnsen I, Pedersen SE, Schönauer M, Nissen KB, Midtgaard SR, Teilum K, Arleth L, Sørensen AT, Bach A, Strømgaard K, Meehan CF, Vægter CB, Gether U, #Madsen KL 'A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain' EMBO Molecular Medicine, 2020, Jun 8;12(6):e11248

Turner C, De Luca M, Wolfheimer J, Hernandez N, Madsen KL, Schmidt HD. Administration of a novel high affinity PICK1 PDZ domain inhibitor attenuates cocaine seeking in rats. Neuropharmacology 2020 Mar 1;164:107901

Erlendsson, S., Thorsen, T. S. and #Madsen, K. L. Supported Cell Membrane Sheets to Monitor Protein Assembly. Bio-protocol 2019 9(18): e3368.

JH Schmidt, M Perslev, L Bukowski, M Stoklund, F Herborg, R Herlo, #Madsen KL ‘Constitutive internalization across therapeutically targeted GPCR s correlates with constitutive activity’ Basic Clin Pharmacol Toxicol. 2019 Jun 22.

VB Kasaragod, TJ Hausrat, N Schaefer, M Kuhn, NR Christensen, Tessmer I, Maric HM, Madsen KL, Sotriffer C, Villmann C, Kneussel M, Schindelin H ‘Elucidating the molecular basis for inhibitory neurotransmission regulation by artemisinins’ Neuron 2019 101 (4), 673-689. e11

Skamris T., Marasini C, Madsen KL, Fodera V, Vestergaard B ‘Early Stage Alpha-Synuclein Amyloid Fibrils are Reservoirs of Membrane-Binding Species’ Scientific reports 2019 9 (1), 1733

Erlendsson S*, Thorsen TS*, Vauquelin G, Ammendrup-Johnsen I, Wirth V, Martinez KL, Teilum K, Gether U, #Madsen KL. ‘Mechanisms of PDZ domain scaffold assembly illuminated by use of supported cell membrane sheets.’ Elife. 2019 Jan 3;8. pii: e39180.

Lund VK, Madsen KL, Kjaerulff O 'Drosophila Rab2 controls endosome–lysosome fusion and LAMP delivery to the endolysosomal pathway Autophagy 2018;14(9):1520-1542

Kathrine Jensen, Gunnar Sørensen, Ditte Dencker, William Owens, Troels Rahbek-Clemmensen, Michael Brett Lever, Annika Runegaard, Nikolaj Riis Christensen, Pia Weikop, Gitta Wörtwein, Anders Fink-Jensen, Kenneth L. Madsen, Lynette Daws, Ulrik Gether, and Mattias Rickhag ‘PICK1-Deficient Mice Exhibit Impaired Response to Cocaine and Dysregulated Dopamine Homeostasis.’ eNeuro, 2018, Jun 11;5(3)

Herlo R, Lund VK, Lycas MD, Jansen AM, Khelashvili G, Andersen RC, Bhatia V, Pedersen TS, Albornoz PBC, Johner N, Ammendrup-Johnsen I, Christensen NR, Erlendsson S, Stoklund M, Larsen JB, Weinstein H, Kjærulff O, Stamou D, Gether U, #Madsen KL. 'An amphipathic helix directs cellular membrane curvature sensing and function of the BAR domain protein PICK1' Cell reports 2018 23 (7), 2056-2069

Falk-Petersen CB, Søgaard R, Madsen KL, Klein AB, Frølund B, Wellendorph P. ‘Development of a Robust Mammalian Cell-based Assay for Studying Recombinant α4 β1/3 δ GABAA Receptor Subtypes.’ Basic Clin Pharmacol Toxicol. 2017 Aug;121(2):119-129

Jacobsen SE, Ammendrup-Johnsen I, Jansen AM, Gether U, Madsen KL, Bräuner-Osborne H. ‘The GPRC6A receptor displays constitutive internalization and sorting to the slow recycling pathway.’ Biol. Chem. 2017 Apr 28;292(17):6910-6926.

A Vuorenpää, TN Jørgensen, AH Newman, KL Madsen, M Scheinin, Ulrik Gether “Differential Internalization Rates and Postendocytic Sorting of the Norepinephrine and Dopamine Transporters Are Controlled by Structural Elements in the N Termini” J. Biol. Chem 2016 291 (11), 5634-5651

S Erlendsson, L Arleth, #KL Madsen “Response to The Challenges of Polydisperse SAXS Data Analysis: Two Different SAXS Studies of PICK1 Produce Different Structural Models” Structure 2015 23 (11), 1969-1970

Karlsen ML, Thorsen TS, Johner N, Ammendrup-Johnsen I, Erlendsson S, Tian X, Simonsen JB, Høiberg-Nielsen R, Christensen NM, Khelashvili G, Streicher W, Teilum K, Vestergaard B, Weinstein H, Gether U, Arleth L, #Madsen KL ‘Structure of dimeric and tetrameric complexes of the BAR domain protein PICK1 determined by small-angle X-ray scattering’ Structure 2015 23 (7), 1258-1270

Pinheiro PS, Jansen AM, de Wit H, Tawfik B, Madsen KL, Verhage M, Gether U, Sørensen JB ‘The BAR Domain Protein PICK1 Controls Vesicle Number and Size in Adrenal Chromaffin Cells’ Journal of Neuroscience 2014 Aug 6; 34 (32): 10688-10700

Erlendsson S, Rathje M, Heidarsson PO, Poulsen FM, Madsen KL, Teilum K, Gether U ‘PICK1 (protein interacting with C-kinase 1) binding promiscuity relies on unconventional PDZ (PSD-95/Discs-large/ZO-1 homology) binding modes for non-class II PDZ ligands’ J. Biol. Chem 2014 Jul 13: jbc. M114. 548743

Rathje M, Fang H, Bachman JL, Gether U, Huganir RL, #Madsen KL ‘Reply to Wilkinson et al.: Concerning the use of pHluorin-tagged GluA2 as a reporter for NMDA-induced AMPA receptor recycling.’ PNAS 2014 Jan 21;111(3):E305

Rathje M, Fang H, Bachman JL, Anggono V, Gether U, Huganir RL, #Madsen KL. AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons. PNAS 2013 Aug 27;110(35):14426-31.

Rickhag M, Owens WA, Winkler MT, Strandfelt KN, Rathje M, Sørensen G, Andresen B, Madsen KL, Jørgensen TN, Wörtwein G, Woldbye DP, Sitte H, Daws LC, Gether U.  Membrane-permeable C-terminal Dopamine Transporter Peptides Attenuate Amphetamine-evoked Dopamine Release. J Biol Chem. 2013 Sep 20;288(38):27534-44.

Nørager NG, Jensen CB, Rathje M, Andersen J, Madsen KL, Kristensen AS, Strømgaard K.  Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons. ACS Chem Biol. 2013 Sep 20;8(9):2033-41.

Sogaard R, Borre L, Braunstein TH, Madsen KL, MacAulay N. Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1. J Biol Chem. 2013 Jul 12;288(28):20195-207.

Holst B*, Madsen KL*, Jansen AM, Jin C, Rickhag M, Lund VK, Jensen M, Bhatia V, Sørensen G, Madsen AN, Xue Z, Møller SK, Woldbye D, Qvortrup K, Huganir R, Stamou D, Kjærulff O, Gether U. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. PLoS Biol. 2013;11(4):e1001542. Epub 2013 Apr 23 *Shared authorship

Rickhag M, Hansen FH, Sørensen G, Strandfelt KN, Andresen B, Gotfryd K, Madsen KL, Vestergaard-Klewe I, Ammendrup-Johnsen I, Eriksen J, Newman AH, Füchtbauer EM, Gomeza J, Woldbye DP, Wörtwein G, Gether U. A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter. Nat Commun. 2013;4:1580.

Madsen KL, Thorsen TS, Rahbek-Clemmensen T, Eriksen J, Gether U. Protein Interacting with C Kinase 1 (PICK1) Reduces Reinsertion Rates of Interaction Partners Sorted to Rab11-dependent Slow Recycling Pathway. J Biol Chem. 2012 Apr 6;287(15):12293-308.

 Ammendrup-Johnsen I, Thorsen TS, Gether U, #Madsen KL. Serine 77 in the PDZ domain of PICK1 is a protein kinase Cα phosphorylation site regulated by lipid membrane binding. Biochemistry. 2012 Jan 17;51(2):586-96.

Thor S. Thorsen, Kenneth L. Madsen, Tino Dyhring, Anders Bach, Dan Peters, Kristian Strømgaard, Lars Christian B. Rønn and Ulrik Gether. A fluorescence polarization based screening assay for identification of small molecule inhibitors of the PICK1 PDZ domain Combinatorial Chemistry and High Throughput Screening. 2011 Aug;14(7):590-600.

Bach A, Stuhr-Hansen N, Thorsen TS, Bork N, Moreira IS, Frydenvang K, Padrah S, Christensen SB, Madsen KL, Weinstein H, Gether U, Strømgaard K. Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1. Org Biomol Chem 2010 Oct 7;8(19):4281-8.

Thorsen TS*, Madsen KL*, Rebola N, Rathje M, Anggono V, Bach A, Moreira IS, Stuhr-Hansen N, Dyhring T, Peters D, Beuming T, Huganir R, Weinstein H, Mulle C, Strømgaard K, Rønn LC, Gether U Identification of a small molecule inhibitor of the PICK1 PDZ domain that inhibits synaptic plasticity. PNAS. 2010 Jan 5;107(1):413-8.  *Shared authorship

Bhatia VK, Madsen KL, Bolinger PY, Kunding A, Hedegård P, Gether U, Stamou D. Amphipathic motifs in BAR domains are essential for membrane curvature sensing EMBO J. 2009 Nov 4;28(21):3303-14.  

Jansen AM, Nässel DR, Madsen KL, Jung AG, Gether U, Kjaerulff O. PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system. J Comp Neurol. 2009 Nov 20;517(3):313-32.

Hatzakis NS, Bhatia VK, Larsen J, Madsen KL, Bolinger PY, Kunding AH, Castillo J, Gether U, Hedegård P, Stamou D. How curved membranes recruit amphipathic helices and protein anchoring motifs. Nat Chem Biol. 2009 Nov;5(11):835-41.

Madsen KL, Eriksen J, Milan-Lobo L, Han DS, Niv MY, Ammendrup-Johnsen I, Henriksen U, Bhatia VK, Stamou D, Sitte HH, McMahon HT, Weinstein H, Gether U. Membrane localization is critical for activation of the PICK1 BAR domain. Traffic. 2008 Aug;9(8):1327-43.

Bassan M, Liu H, Madsen KL, Armsen W, Zhou J, Desilva T, Chen W, Paradise A, Brasch MA, Staudinger J, Gether U, Irwin N, Rosenberg PA. Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1. Eur J Neurosci. 2008 Jan;27(1):66-82.

Sogaard R, Werge TM, Bertelsen C, Lundbye C, Madsen KL, Nielsen CH, Lundbaek JA. GABA(A) receptor function is regulated by lipid bilayer elasticity. Biochemistry. 2006 Oct 31;45(43):13118-29. 

Madsen KL, Beuming T, Niv MY, Chang CW, Dev KK, Weinstein H, Gether U. Molecular determinants for the complex binding specificity of the PDZ domain in PICK1. J Biol Chem. 2005 May 27;280(21):20539-48.

Bjerggaard C, Fog JU, Hastrup H, Madsen K, Loland CJ, Javitch JA, Gether U. Surface targeting of the dopamine transporter involves discrete epitopes in the distal C terminus but does not require canonical PDZ domain interactions. J Neurosci. 2004 Aug 4;24(31):7024-36. 

Peer reviewed reviews and commentaries

Jensen KL, Jensen SB, #Madsen KL ’A mechanistic overview of approaches for the treatment of psychostimulant dependence’ Front Pharmacology. 2022 Sep 8;13:854176. Review

Sørensen AT, Rombach J, Gether U, #Madsen KL. ‘The Scaffold Protein PICK1 as a Target in Chronic Pain.’ Cells. 2022 Apr 7;11(8):1255. Review

Madsen KL and Dreyer JK. ‘Striatal neurons get a kick out of dopamine’ Journal of Physiology. 2017, Dec 15;595(24):7271-7272. Commentary

#Madsen KL, Herlo R. ‘Recursive Alterations of the Relationship between Simple Membrane Geometry and Insertion of Amphiphilic Motifs.’ Membranes. 2017, Feb 8;7(1):6 Review

Erlendsson S, #Madsen KL. ‘Membrane Binding and Modulation of the PDZ Domain of PICK1.’ Membranes 2015, Oct 16;5(4):597-615, Review

Madsen KL, Bhatia VK, Gether U, Stamou D BAR domains, amphipathic helices and membrane-anchored proteins use the same mechanism to sense membrane curvature., FEBS Lett. 2010, May 3;584(9):1848-55 Review.