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Activity‐dependent endocytic sorting of kainate receptors to recycling or degradation pathways
Author(s) -
Martin Stéphane,
Henley Jeremy M
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600483
Subject(s) - biology , kainate receptor , synaptic plasticity , neuroscience , receptor , genetics , ampa receptor , glutamate receptor
Kainate receptors (KARs) play important roles in the modulation of neurotransmission and plasticity, but the mechanisms that regulate their surface expression and endocytic sorting remain largely unknown. Here, we show that in cultured hippocampal neurons the surface expression of GluR6‐containing KARs is dynamically regulated. Furthermore, internalized KARs are sorted into recycling or degradative pathways depending on the endocytotic stimulus. Kainate activation causes a Ca 2+ ‐ and PKA‐independent but PKC‐dependent internalization of KARs that are targeted to lysosomes for degradation. In contrast, NMDAR activation evokes a Ca 2+ ‐, PKA‐ and PKC‐dependent endocytosis of KARs to early endosomes with subsequent reinsertion back into the plasma membrane. These results demonstrate that GluR6‐containing KARs are subject to activity‐dependent endocytic sorting, a process that provides a mechanism for both rapid and chronic changes in the number of functional receptors.