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Published online July 7, 2008
doi:10.1083/jcb.200712094
The Journal of Cell Biology, Vol. 182, No. 1, 141-155
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Chao et al.
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Article

 SUMOylation of the MAGUK protein CASK regulates dendritic spinogenesis

Hsu-Wen Chao1,2, Chen-Jei Hong1,2, Tzyy-Nan Huang1,2, Yi-Ling Lin2,3, and Yi-Ping Hsueh1,2,3

1 Graduate Institute of Life Science, National Defense Medical Center, 2 Institute of Molecular Biology, Academia Sinica, and 3 Graduate Institute of Genome Sciences, National Yang-Ming University, Taipei 11529, Taiwan

Correspondence to Yi-Ping Hsueh: yph{at}gate.sinica.edu.tw

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.

Abbreviations used in this paper: CaMK, calcium/calmodulin-dependent protein kinase; CASK, calcium/calmodulin-dependent serine protein kinase; DIV, day in vitro; KS, Kolmogorov-Smirnov; MAGUK, membrane-associated guanylate kinase; MEF2, myocyte enhancer factor 2; shRNA, short hairpin RNA; SUMO, small ubiquitin-like modifier; SynCAM, synaptic cell adhesion molecule; TTX, tetrodotoxin.

© 2008 Chao et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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