Unknown

Dataset Information

0

Postsynaptic kainate receptor recycling and surface expression are regulated by metabotropic autoreceptor signalling.


ABSTRACT: Kainate receptors (KARs) play fundamentally important roles in controlling synaptic function and regulating neuronal excitability. Postsynaptic KARs contribute to excitatory neurotransmission but the molecular mechanisms underlying their activity-dependent surface expression are not well understood. Strong activation of KARs in cultured hippocampal neurons leads to the downregulation of postsynaptic KARs via endocytosis and degradation. In contrast, low-level activation augments postsynaptic KAR surface expression. Here, we show that this increase in KARs is due to enhanced recycling via the recruitment of Rab11-dependent, transferrin-positive endosomes into spines. Dominant-negative Rab11 or the recycling inhibitor primaquine prevents the kainate-evoked increase in surface KARs. Moreover, we show that the increase in surface expression is mediated via a metabotropic KAR signalling pathway, which is blocked by the protein kinase C inhibitor chelerythrine, the calcium chelator BAPTA and the G-protein inhibitor pertussis toxin. Thus, we report a previously uncharacterized positive feedback system that increases postsynaptic KARs in response to low- or moderate-level agonist activation and can provide additional flexibility to synaptic regulation.

SUBMITTER: Gonzalez-Gonzalez IM 

PROVIDER: S-EPMC3744763 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Postsynaptic kainate receptor recycling and surface expression are regulated by metabotropic autoreceptor signalling.

González-González Inmaculada M IM   Henley Jeremy M JM  

Traffic (Copenhagen, Denmark) 20130425 7


Kainate receptors (KARs) play fundamentally important roles in controlling synaptic function and regulating neuronal excitability. Postsynaptic KARs contribute to excitatory neurotransmission but the molecular mechanisms underlying their activity-dependent surface expression are not well understood. Strong activation of KARs in cultured hippocampal neurons leads to the downregulation of postsynaptic KARs via endocytosis and degradation. In contrast, low-level activation augments postsynaptic KAR  ...[more]

Similar Datasets

| S-EPMC8441151 | biostudies-literature
| S-EPMC2662304 | biostudies-literature
| S-EPMC1851615 | biostudies-literature
| S-EPMC2756730 | biostudies-literature
| S-EPMC2746435 | biostudies-literature
| S-EPMC2804989 | biostudies-literature
2023-09-18 | GSE134810 | GEO
| S-EPMC7076251 | biostudies-literature
| S-EPMC3533475 | biostudies-literature
| S-EPMC5489663 | biostudies-literature