KAR ja GlyR , SENP1 ja PKC-sumoylaatiosta riippuva säätelytie tärkeä neuronin ärtyvyydelle

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199113/

Nat Commun. 2014 Sep 19; 5: 4980.

Published online 2014 Sep 19. doi: 10.1038/ncomms5980

PMCID: PMC4199113

PMID: 25236484

Kainate receptor activation induces glycine receptor endocytosis through PKC deSUMOylation

Hao Sun,^1,* Li Lu,^1,* Yong Zuo,^1,* Yan Wang,¹ Yingfu Jiao,¹ Wei-Zheng Zeng,¹ Chao Huang,² Michael X. Zhu,³ Gerald W. Zamponi,⁴ Tong Zhou,⁵ Tian-Le Xu,¹ Jinke Cheng,¹ and Yong Li^a,1

 Abstract

Surface expression and regulated endocytosis of glycine receptors (GlyRs) play a critical function in balancing neuronal excitability. 

SUMOylation (SUMO modification) is of critical importance for maintaining neuronal function in the central nervous system. 

Here we show that activation of kainate receptors (KARs) causes GlyR endocytosis in a calcium- and protein kinase C (PKC)-dependent manner, leading to reduced GlyR-mediated synaptic activity in cultured spinal cord neurons and the superficial dorsal horn of rat spinal cord slices. 

This effect requires SUMO1/sentrin-specific peptidase 1 (SENP1)-mediated deSUMOylation of PKC, indicating that the crosstalk between KARs and GlyRs relies on the SUMOylation status of PKC. SENP1-mediated deSUMOylation of PKC is involved in the kainate-induced GlyR endocytosis and thus plays an important role in the anti-homeostatic regulation between excitatory and inhibitory ligand-gated ion channels.

 Altogether, we have identified a SUMOylation-dependent regulatory pathway for GlyR endocytosis, which may have important physiological implications for proper neuronal excitability.


Taken together, these findings support the mechanism by which SENP1 regulates kainate-induced GlyR endocytosis via changing the SUMOylation status and activity of PKC.