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PMID: 18606847 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

SUMOylation of the MAGUK protein CASK regulates dendritic spinogenesis.

The Journal of cell biology ·Vol. 182 ·No. 1 ·2008-07-14 ·Pages 141-55

Chao HW, Hong CJ, Huang TN, Lin YL, Hsueh YP

Abstract

Membrane-associated guanylate kinase (MAGUK) proteins interact with several synaptogenesis-triggering adhesion molecules. However, direct evidence for the involvement of MAGUK proteins in synapse formation is lacking. In this study, we investigate the function of calcium/calmodulin-dependent serine protein kinase (CASK), a MAGUK protein, in dendritic spine formation by RNA interference. Knockdown of CASK in cultured hippocampal neurons reduces spine density and shrinks dendritic spines. Our analysis of the time course of RNA interference and CASK overexpression experiments further suggests that CASK stabilizes or maintains spine morphology. Experiments using only the CASK PDZ domain or a mutant lacking the protein 4.1-binding site indicate an involvement of CASK in linking transmembrane adhesion molecules and the actin cytoskeleton. We also find that CASK is SUMOylated. Conjugation of small ubiquitin-like modifier 1 (SUMO1) to CASK reduces the interaction between CASK and protein 4.1. Overexpression of a CASK-SUMO1 fusion construct, which mimicks CASK SUMOylation, impairs spine formation. Our study suggests that CASK contributes to spinogenesis and that this is controlled by SUMOylation.

MeSH Terms
Animals Binding Sites COS Cells Chlorocebus aethiops Cytoskeletal Proteins/metabolism Dendrites/enzymology Guanylate Kinases/chemistry,metabolism Humans Membrane Proteins/metabolism Mice Neuropeptides/metabolism Protein Structure, Tertiary Protein Transport Rats Small Ubiquitin-Related Modifier Proteins/metabolism Synapses/enzymology Time Factors
Chemicals
Cytoskeletal Proteins Membrane Proteins Neuropeptides Small Ubiquitin-Related Modifier Proteins erythrocyte membrane protein band 4.1-like 1 CASK kinases Guanylate Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chao Hsu-Wen
Graduate Institute of Life Science, National Defense Medical Center, National Yang-Ming University, Taipei 11529, Taiwan.
Hong Chen-Jei
Huang Tzyy-Nan
Lin Yi-Ling
Hsueh Yi-Ping
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200712094
Published
2008-07-14
Epub
2008-00-07
Pages
141-55
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2447900
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200712094 PMC Full Text View journal details
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