TY - JOUR

T1 - Expression of the Ly-6 family proteins Lynx1 and Ly6H in the rat brain is compartmentalized, cell-type specific, and developmentally regulated

AU - Thomsen, Morten Skøtt

AU - Cinar, Betül

AU - Jensen, Majbrit Myrup

AU - Lyukmanova, Ekaterina N

AU - Shulepko, Mikhail A

AU - Tsetlin, Victor

AU - Klein, Anders Bue

AU - Mikkelsen, Jens D

PY - 2014/11/17

Y1 - 2014/11/17

N2 - The Ly-6 superfamily of proteins, which affects diverse processes in the immune system, has attracted renewed attention due to the ability of some Ly-6 proteins to bind to and modulate the function of neuronal nicotinic acetylcholine receptors (nAChRs). However, there is a scarcity of knowledge regarding the distribution and developmental regulation of these proteins in the brain. We use protein cross-linking and synaptosomal fractions to demonstrate that the Ly-6 proteins Lynx1 and Ly6H are membrane-bound proteins in the brain, which are present on the cell surface and localize to synaptic compartments. We further estimate the amount of Lynx1 in the rat cortex using known amounts of a heterologously expressed soluble Lynx1 variant (ws-Lynx1) to be approximately 8.6 ng/μg total protein, which is in line with the concentrations of ws-Lynx1 required to affect nAChR function. In addition, we demonstrate that Lynx1 and Ly6H are expressed in cultured neurons, but not cultured micro- or astroglial cultures. In addition, Lynx1, but not Ly6H was detected in the CSF. Finally, we show that the Ly-6 proteins Lynx1, Lynx2, Ly6H, and PSCA, display distinct expression patterns during postnatal development in the rat frontal cortex and hippocampus at the mRNA and protein level, and that this is paralleled to some degree by the expression of the nAChR subunits α2, α4, α7 and β2. Our results demonstrate a developmental pattern, localization, and concentration of Ly-6 proteins in the brain, which support a role for these proteins in the modulation of signaling at synaptic membranes.

AB - The Ly-6 superfamily of proteins, which affects diverse processes in the immune system, has attracted renewed attention due to the ability of some Ly-6 proteins to bind to and modulate the function of neuronal nicotinic acetylcholine receptors (nAChRs). However, there is a scarcity of knowledge regarding the distribution and developmental regulation of these proteins in the brain. We use protein cross-linking and synaptosomal fractions to demonstrate that the Ly-6 proteins Lynx1 and Ly6H are membrane-bound proteins in the brain, which are present on the cell surface and localize to synaptic compartments. We further estimate the amount of Lynx1 in the rat cortex using known amounts of a heterologously expressed soluble Lynx1 variant (ws-Lynx1) to be approximately 8.6 ng/μg total protein, which is in line with the concentrations of ws-Lynx1 required to affect nAChR function. In addition, we demonstrate that Lynx1 and Ly6H are expressed in cultured neurons, but not cultured micro- or astroglial cultures. In addition, Lynx1, but not Ly6H was detected in the CSF. Finally, we show that the Ly-6 proteins Lynx1, Lynx2, Ly6H, and PSCA, display distinct expression patterns during postnatal development in the rat frontal cortex and hippocampus at the mRNA and protein level, and that this is paralleled to some degree by the expression of the nAChR subunits α2, α4, α7 and β2. Our results demonstrate a developmental pattern, localization, and concentration of Ly-6 proteins in the brain, which support a role for these proteins in the modulation of signaling at synaptic membranes.

U2 - 10.1007/s00429-013-0611-x

DO - 10.1007/s00429-013-0611-x

M3 - Journal article

C2 - 23860910

VL - 219

SP - 1923

EP - 1934

JO - Brain Structure and Function

JF - Brain Structure and Function

SN - 1863-2653

IS - 6

ER -