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Free Content The Role of the MAGUK Protein CASK in Neural Development and Synaptic Function

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CASK, which belongs to the family of membrane-associated guanylate kinase (MAGUK) proteins, is recognized as a multidomain scaffolding protein highly expressed in the mammalian nervous system. MAGUK proteins generally target to neuronal synapses and regulate trafficking, targeting, and signaling of ion channels. However, CASK is a unique MAGUK protein in several respects. It not only plays a role in synaptic protein targeting but also contributes to neural development and regulation of gene expression. Several CASK-interacting proteins have been identified from yeast two-hybrid screening and biochemical isolation. These proteins, whose interactions with CASK are reviewed here, include the Parkinson's disease molecule parkin, the adhesion molecule neurexin, syndecans, calcium channel proteins, the cytoplasmic adaptor protein Mint1, Veli/mLIN-7/MALS, SAP97, caskin and CIP98, transcription factor Tbr-1, and nucleosome assembly protein CINAP. More important, CASK may form different complexes with different binding partners and perform different functions. Among these interactions, CASK, Tbr-1, and CINAP can form a transcriptional complex regulating gene expression. Reelin and NMDAR subunit 2b (NR2b) genes have been identified as Tbr-1 target genes. Reelin is critical for neural development. NR2b is an important subunit of NMDAR, which plays important roles in neural function and neurological diseases. Regulation of reelin and NR2b expression suggests the potential roles of the Tbr-1-CASK-CINAP complex in neural activity, development, and disease. The functions of these CASK protein complexes are also discussed in detail in this review.

Keywords: Synapse; cerebral cortex; gene expression; hippocampus; neural development; postsynaptic density; transcription

Document Type: Research Article


Affiliations: Institute of Molecular Biology,Academia Sinica, 128 Academia Rd, Sec. 2, Taipei, Taiwan, 11529,Republic of China.

Publication date: July 1, 2006

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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