Regulation of mGluR7 trafficking by SUMOylatio in neurons

Protein SUMOylation is a post-translationalmodification by which SmallUbiquitin-like MOdifier (SUMO) proteins are covalently linked to the lysine residues of target proteins via an enzymatic cascade. It has been reported that SUMOylation of synaptic proteins plays important regulatory roles in synapse formation, axonal mRNA transport, channel activity, and receptorendocytosis. The metabotropic glutamate receptor type 7 (mGluR7), a presynaptic G protein-coupled receptor modulates excitatoryneurotransmission and synaptic plasticity by inhibiting neurotransmitter release. mGluR7 at Lys889 has been proposed to be modified by SUMO proteins invitroassays, and a consensus motiffor SUMO conjugation is conserved in the C-terminus of mGluR7. However, a recent study has failed to demonstrate the SUMO conjugation of full-length mGluR7 in mammalian cells and neurons. Here we have explored whether mGluR7 is a target of SUMOylation. Using biochemical approaches coupled with confocal imaging, we find that mGluR7 at Lys889, the sole SUMOylation site on the C-terminus of mGluR7 is a target of SUMO conjugation both by SUMO-1and SUMO-2/3 in HEK293T cells. The SUMOylation of mGluR7 is prevented by SUMO-specific isopeptidase SENP-1. Furthermore, the SUMOylation of mGluR7mediated by SUMO-1 and SUMO-2/3 is identified in primary cortical neurons. Of particular interest, treatment of mGluR7 with an agonist,L-AP4 leads to a profound decrease of SUMO-1 conjugation of mGluR7, whereas there is no change of agonist-induced SUMO-2/3 conjugation of mGluR7. In addition, we find that mutation of mGluR7 at Lys889 to Arg markedly increases mGluR7 internalization in hippocampal neurons. Overexpression of SENP-1 leads to increased internalization of mGluR7, whereas SENP-1Cys603Ser, a catalytic inactive mutant has no effects, suggesting that endocytosis of mGluR7 is enhanced by reduced SUMO conjugation of mGluR7. Taken together, these data support a modelin which SUMOylation of mGluR7 at Lys889 for stable surface expression of mGluR7 in neurons.

Author dc:creator

• 최, 지희

Contributors dc:contributor

• 서, 영호
• 대학원 의생명과학과
• 201224139

• 수모 단백질
• 수모화 반응
• mGluR7 수용체
• 전사 후 변형 과정
• SUMO
• SUMOylatio
• Post-translational modification

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000017404
000000017404

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/10867