Article
- The EMBO Journal (2007) 26, 4359 - 4367
- doi:10.1038/sj.emboj.7601865
Published online: 27 September 2007
Subject Category:
PKC-dependent autoregulation of membrane kainate receptors
Rocío Riveraa, José Luis Rozasab and Juan Lerma
- Cellular and Systems Neurobiology, Instituto de Neurociencias de Alicante, CSIC-UMH, San Juan de Alicante, Spain
Correspondence to:
Juan Lerma, Cellular and Systems Neurobiology, Instituto de Neurociencias de Alicante, CSIC-UMH, Aptdo 18, San Juan de Alicante, Alicante 3550, Spain. Tel.: +34965919239; Fax: +34965919561; E-mail: jlerma@umh.es
aThese authors contributed equally to this work
bPresent address: Department Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla 41009, Spain
Received 21 March 2007; Accepted 30 August 2007
Abstract
Agonists of kainate receptors (KARs) cause both the opening of the associated ion channels and the activation of signalling pathways driven by G-proteins and PKC. Here we report the existence of an unknown mechanism of KAR autoregulation, involving the interplay of this two signalling mechanisms. Repetitive activation of native KARs evoked the rundown of the ionotropic responses in a manner that was dependent on the activation of PKC. Experiments on recombinant GluR5 expressed in neuroblastoma cells indicated that KARs trigger the activation of PKC and induce the internalization of membrane receptors. This phenomenon depends on the PKC-mediated phosphorylation of serines 879 and 885 of the GluR5-2b subunits, since mutation of these two residues abolished internalization. These results reveal that the non-canonical signalling of KARs is associated with a sensitive mechanism that detects afferent activity. Such a mechanism represents an active way to limit overactivation of the KAR system, by regulating the number of KARs in the cell membrane.
Keywords:
- dorsal root ganglia cells,
- endocytosis,
- GluR5,
- glutamate receptors,
- trafficking
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