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The neuronal glycine transporter GLYT2 associates with membrane rafts: functional modulation by lipid environment
Author(s) -
Núñez Enrique,
AlonsoTorres Pablo,
Fornés Amparo,
Aragón Carmen,
LópezCorcuera Beatriz
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05292.x
Subject(s) - lipid raft , glycine receptor , microbiology and biotechnology , biology , biochemistry , chemistry , glycine , signal transduction , amino acid
The neuronal glycine transporter GLYT2 is a plasma membrane protein that removes the neurotransmitter glycine from the synaptic cleft, thereby aiding the pre‐synaptic terminal reloading and the termination of the glycinergic signal. Missense mutations in the gene encoding GLYT2 (SLC6A5) cause hyperekplexia in humans. The activity of GLYT2 seems to be highly regulated. In this report, we demonstrate that GLYT2 is associated with membrane rafts in the plasma membrane of brainstem terminals and neurons. The transporter is localized to Triton X‐100‐insoluble light synaptosomal membranes together with flotillin‐1, a marker protein for membrane rafts, in a methyl‐β‐cyclodextrin (MβCD)‐sensitive manner. In brainstem primary neurons, the GLYT2 punctuate pattern visualized by confocal microscopy was modified by cholesterol depletion with MβCD, unlike other non‐raft neuronal markers. GLYT2‐associated gold particles were observed by electron microscopy on purified rafts from brainstem synaptosomes. Furthermore, either in brainstem terminals and cultured neurons, the pharmacological reduction of the levels of raft components, cholesterol and sphingomyelin, impairs both the association of GLYT2 with membrane rafts and its transport activity. Thus, GLYT2 may require membrane raft location for optimal function, and therefore the lipid environment may constitute a new mechanism to modulate GLYT2.