SUMOylation of the MAGUK protein CASK regulates dendritic spinogenesis

Hsu Wen Chao, Chen Jei Hong, Tzyy Nan Huang, Yi G. Lin, Yi Ping Hsueh

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87 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)141-155
Number of pages15
JournalJournal of Cell Biology
Issue number1
Publication statusPublished - Jul 14 2008
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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