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PMID: 16672654 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

ARF6 and EFA6A regulate the development and maintenance of dendritic spines.

Choi S, Ko J, Lee JR, Lee HW, Kim K, Chung HS, Kim H, Kim E

Abstract

The cellular and molecular mechanisms underlying the development and maintenance of dendritic spines are not fully understood. ADP-ribosylation factor 6 (ARF6) is a small GTPase known to regulate actin remodeling and membrane traffic. Here, we report involvement of ARF6 and exchange factor for ARF6 (EFA6A) in the regulation of spine development and maintenance. An active form of ARF6 promotes the formation of dendritic spines at the expense of filopodia. EFA6A promotes spine formation in an ARF6 activation-dependent manner. Knockdown of ARF6 and EFA6A by small interfering RNA decreases spine formation. Live imaging indicates that ARF6 knockdown decreases the conversion of filopodia to spines and the stability of early spines. The spine-promoting effect of ARF6 is partially blocked by Rac1. ARF6 and EFA6A protect mature spines from inactivity-induced destabilization. These results suggest that ARF6 and EFA6A may regulate the conversion of filopodia to spines and the stability of both early and mature spines.

MeSH Terms
ADP-Ribosylation Factor 6 ADP-Ribosylation Factors/pharmacology,physiology Anesthetics, Local/pharmacology Animals Animals, Newborn Blotting, Northern/methods Brain/growth & development,metabolism Cells, Cultured Dendritic Spines/drug effects,physiology Diagnostic Imaging/methods Disks Large Homolog 4 Protein Drug Interactions Embryo, Mammalian Enzyme Activation Gene Expression Regulation, Developmental/physiology Green Fluorescent Proteins/metabolism Guanine Nucleotide Exchange Factors/pharmacology,physiology Hippocampus/cytology Immunohistochemistry/methods Intracellular Signaling Peptides and Proteins/metabolism Membrane Proteins/metabolism Mutagenesis/physiology Neurons/cytology Pseudopodia/drug effects,physiology RNA, Small Interfering/pharmacology Rats Tetrodotoxin/pharmacology Time Factors Transfection/methods
Chemicals
ADP-Ribosylation Factor 6 Anesthetics, Local Disks Large Homolog 4 Protein Dlg4 protein, rat Guanine Nucleotide Exchange Factors Intracellular Signaling Peptides and Proteins Membrane Proteins Psd protein, rat RNA, Small Interfering Green Fluorescent Proteins Tetrodotoxin ADP-Ribosylation Factors Arf6 protein, rat
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Choi Seungwon
National Creative Research Initiative Center for Synaptogenesis, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Ko Jaewon
Lee Jae-Ran
Lee Hyun Woo
Kim Karam
Chung Hye Sun
Kim Hyun
Kim Eunjoon
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2006-05-03
Pages
4811-9
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6674147
Subset
IM
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