Our research efforts revolves around Drosophila (the fruit fly), a powerful genetic model system. The focus is basic cell biology, but with a keen view on medical relevance.
Our research efforts revolves around Drosophila (the fruit fly), a powerful genetic model system. The focus is basic cell biology, but with a keen view on medical relevance. A long-standing interest is the BAR domain endophilin (ref. 1), a synaptic protein involved in retrieval of synaptic vesicles and with a critical role in the ability of synapses to maintain prolonged activity (group leader first-authored seminal paper on endophilin function, published in Cell 2002). Most recently, we have:
- Identified hormonal/metabolic defects in Drosophila and mice mutant for the BAR domain protein PICK1. An extensive analysis revealed a deficiency in the biogenesis of peptide hormones such as insulin and growth hormone in PICK1 null animals (ref. 1 below).
- Demonstrated that blocking the formation of complex glycosphingolipids during development induces overgrowth of glial cells (ref. 2). In a follow-up study this effect was related to disinhibition of growth signaling mediated by Insulin and Fibroblast Growth Factor Receptors (ref. 3).
- Ongoing projects concern the regulation of the activity of the BAR domain protein endophilin. Morover, we analyze the role of specific proteins in the biogenesis of lysosomes, in neurons and other cells. Besides being of fundamental cell biological importance, this topic is of interest because lysosomal breakdown of toxic protein aggregates constitutes an important defense mechanism in neurodegenerative diseases.
- PICK1-Deficiency Impairs Secretory Vesicle Biogenesis and Leads to Growth Retardation and Decreased Glucose Tolerance. B Holst*, KL Madsen, AM Jansen, C Jin, M Rickhag, VK. Lund, M Jensen, V Bhatia, G Sørensen, AN. Madsen, Z Xue, SK Møller, D Woldbye, K Qvortrup, R Huganir, D Stamou, O Kjærulff*, U Gether*. PLoS Biology 2013, 11(4): e1001542.
- K Dahlgaard, A Jung, K Qvortrup, H Clausen, O Kjaerulff* and H Wandall*. A neurofibromatosis-like phenotype in Drosophila lacking glycosylceramide extension. Proceedings of the National Academy of Sciences USA 2012, 109 (18): 6987-92.
- Mactosylceramide Prevents Glial Cell Overgrowth by Inhibiting Insulin and Fibroblast Growth Factor Receptor Signaling. Gerdøe-Kristensen S, Lund VK, Wandall HH, Kjaerulff O*. Journal of Cellular Physiology. 2016 Dec 26. doi: 10.1002/jcp.25762.
- Kjaerulff O*, Brodin L, Jung A. The structure and function of endophilin proteins. Cell Biochemistry and Biophysics 2011, 60:137-54.
*Author(s) for correspondence.