Article
- The EMBO Journal (2004) 23, 4749 - 4759
- doi:10.1038/sj.emboj.7600483
Published online: 18 November 2004
Subject Categories:
Activity-dependent endocytic sorting of kainate receptors to recycling or degradation pathways
Stéphane Martin and Jeremy M Henley
- Department of Anatomy, MRC Centre for Synaptic Plasticity, School of Medical Sciences, University Walk, University of Bristol, Bristol, UK
Correspondence to:
Jeremy M Henley, Department of Anatomy, MRC Centre for Synaptic Plasticity, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK. Tel.: +44 117 954 6449; Fax: +44 117 929 1687; E-mail: j.m.henley@bris.ac.uk
Received 16 September 2004; Accepted 22 October 2004
Abstract
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 Ca2+- and PKA-independent but PKC-dependent internalization of KARs that are targeted to lysosomes for degradation. In contrast, NMDAR activation evokes a Ca2+-, 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.
Keywords:
- endocytosis,
- kainate receptors,
- receptor recycling,
- surface expression
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