Journal
BRAIN STRUCTURE & FUNCTION
Volume 219, Issue 6, Pages 1923-1934Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00429-013-0611-x
Keywords
Nicotinic acetylcholine receptor; Allosteric modulator; Frontal cortex; Hippocampus; Synaptosomes; Lynx1; Lynx2; Ly6H; PSCA
Categories
Funding
- Danish Medical Research Council
- Danish Strategic Research Council
- Lundbeck Foundation
- NOVO Nordisk Foundation
- Danish Ministry of Science, Innovation and Higher Education
- Russian Academy of Sciences (Program Molecular and Cell Biology'')
- Ministry of Science and Education [8268]
- Russian Foundation for Basic Research
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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/mu g 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 alpha 2, alpha 4, alpha 7 and beta 2. 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.
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