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PMID: 18987319 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Regulation of postsynaptic AMPA responses by synaptojanin 1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 45 ·2008-11-11 ·Pages 17561-6

Gong LW, De Camilli P

Abstract

Endocytosis of postsynaptic AMPA receptors is a mechanism through which efficiency of neurotransmission is regulated. We have genetically tested the hypothesis that synaptojanin 1, a phosphoinositide phosphatase implicated in the endocytosis of synaptic vesicles presynaptically, may also function in the endocytosis of AMPA receptors postsynaptically. Electrophysiological recordings of cultured hippocampal neurons showed that miniature excitatory postsynaptic current amplitudes were larger in synaptojanin 1 knockout (KO) neurons because of an increase of surface-exposed AMPA receptors. This change did not represent an adaptive response to decreased presynaptic release in KO cultures and was rescued by the expression of wild type, but not catalytically inactive synaptojanin 1, in the postsynaptic neuron. NMDA-induced internalization of pHluorin-tagged AMPA receptors (GluR2) was impaired in KO neurons. These results reveal a function of synaptojanin 1 in constitutive and triggered internalization of AMPA receptors and thus indicate a role for phosphatidylinositol(4,5)-bisphosphate metabolism in the regulation of postsynaptic AMPA responses.

MeSH Terms
Analysis of Variance Animals Electrophysiology Endocytosis/physiology Green Fluorescent Proteins Hippocampus/metabolism Mice Mice, Knockout Nerve Tissue Proteins/genetics,metabolism Phosphatidylinositol 4,5-Diphosphate/metabolism Phosphoric Monoester Hydrolases/genetics,metabolism Receptors, AMPA/metabolism Synaptic Transmission/physiology
Chemicals
Nerve Tissue Proteins PHluorin Phosphatidylinositol 4,5-Diphosphate Receptors, AMPA Green Fluorescent Proteins synaptojanin Phosphoric Monoester Hydrolases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gong Liang-Wei
Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.
De Camilli Pietro
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0809221105
Published
2008-11-11
Epub
2008-00-05
Pages
17561-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2579885
Subset
IM
Grants
NCI NIH HHS · P01 CA046128 · United States
NIDA NIH HHS · P30 DA018343 · United States
NIDDK NIH HHS · DK45735 · United States
NCI NIH HHS · CA46128 · United States
NIDDK NIH HHS · P30 DK045735 · United States
NINDS NIH HHS · R01 NS036251 · United States
Howard Hughes Medical Institute · United States
NIDA NIH HHS · DA018343 · United States
NINDS NIH HHS · NS36251 · United States
NINDS NIH HHS · R37 NS036251 · United States
Corrections
CommentIn
PMID: 18997011
External Links
PubMed source DOI: 10.1073/pnas.0809221105 PMC Full Text View journal details
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