Signal peptide represses GluK1 surface and synaptic trafficking through binding to amino-terminal domain.

Autor:	Duan GF; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Nanjing Drum Tower Hospital, The Affliated Hospital of Nanjing University Medical School, and Minister of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, 210032, China., Ye Y; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China., Xu S; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China., Tao W; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 94143, CA, USA., Zhao S; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China., Jin T; Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, 230007, China., Nicoll RA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 94143, CA, USA.; Department of Physiology, University of California, San Francisco, 94143, CA, USA., Shi YS; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Nanjing Drum Tower Hospital, The Affliated Hospital of Nanjing University Medical School, and Minister of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, 210032, China. yunshi@nju.edu.cn.; Institute for Brain Sciences, Nanjing University, Nanjing, 210032, China. yunshi@nju.edu.cn., Sheng N; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China. shengnengyin@mail.kiz.ac.cn.; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China. shengnengyin@mail.kiz.ac.cn.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2018 Nov 19; Vol. 9 (1), pp. 4879. Date of Electronic Publication: 2018 Nov 19.
DOI:	10.1038/s41467-018-07403-7
Abstrakt:	Kainate-type glutamate receptors play critical roles in excitatory synaptic transmission and synaptic plasticity in the brain. GluK1 and GluK2 possess fundamentally different capabilities in surface trafficking as well as synaptic targeting in hippocampal CA1 neurons. Here we find that the excitatory postsynaptic currents (EPSCs) are significantly increased by the chimeric GluK1(SP GluK2 ) receptor, in which the signal peptide of GluK1 is replaced with that of GluK2. Coexpression of GluK1 signal peptide completely suppresses the gain in trafficking ability of GluK1(SP GluK2 ), indicating that the signal peptide represses receptor trafficking in a trans manner. Furthermore, we demonstrate that the signal peptide directly interacts with the amino-terminal domain (ATD) to inhibit the synaptic and surface expression of GluK1. Thus, we have uncovered a trafficking mechanism for kainate receptors and propose that the cleaved signal peptide behaves as a ligand of GluK1, through binding with the ATD, to repress forward trafficking of the receptor.
Databáze:	MEDLINE
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