SUMOylation of the MAGUK protein CASK regulates dendritic spinogenesis.
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.
Chao
Hsu-Wen
HW
Graduate Institute of Life Science, National Defense Medical Center, National Yang-Ming University, Taipei 11529, Taiwan.
Hong
Chen-Jei
CJ
Huang
Tzyy-Nan
TN
Lin
Yi-Ling
YL
Hsueh
Yi-Ping
YP
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003712:Dendrites / Q000201:enzymology*; D051528:Guanylate Kinases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology; D013997:Time Factors
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D025841:Small Ubiquitin-Related Modifier Proteins; C120557:erythrocyte membrane protein band 4.1-like 1; C106868:CASK kinases; D051528:Guanylate Kinases