Research article summary (published 30 May 2002):

CASK participates in alternative tripartite complexes in which Mint 1 competes for binding with caskin 1, a novel CASK-binding protein.

Full Abstract

CASK, an adaptor protein of the plasma membrane, is composed of an N-terminal calcium/calmodulin-dependent protein (CaM) kinase domain, central PSD-95, Dlg, and ZO-1/2 domain (PDZ) and Src homology 3 (SH3) domains, and a C-terminal guanylate kinase sequence. The CaM kinase domain of CASK binds to Mint 1, and the region between the CaM kinase and PDZ domains interacts with Velis, resulting in a tight tripartite complex. CASK, Velis, and Mint 1 are evolutionarily conserved in Caenorhabditis elegans, in which homologous genes (called lin-2, lin-7, and lin-10) are required for vulva development. We now demonstrate that the N-terminal CaM kinase domain of CASK binds to a novel brain-specific adaptor protein called Caskin 1. Caskin 1 and a closely related isoform, Caskin 2, are multidomain proteins containing six N-terminal ankyrin repeats, a single SH3 domain, and two sterile alpha motif domains followed by a long proline-rich sequence and a short conserved C-terminal domain. Unlike CASK and Mint 1, no Caskin homolog was detected in C. elegans. Immunoprecipitations showed that Caskin 1, like Mint 1, is stably bound to CASK in the brain. Affinity chromatography experiments demonstrated that Caskin 1 coassembles with CASK on the immobilized cytoplasmic tail of neurexin 1, suggesting that CASK and Caskin 1 coat the cytoplasmic tails of neurexins and other cell-surface proteins. Detailed mapping studies revealed that Caskin 1 and Mint 1 bind to the same site on the N-terminal CaM kinase domain of CASK and compete with each other for CASK binding. Our data suggest that in the vertebrate brain, CASK and Velis form alternative tripartite complexes with either Mint 1 or Caskin 1 that may couple CASK to distinct downstream effectors.

Author information

Author/s: Tabuchi, Katsuhiko (K); Biederer, Thomas (T); Butz, Stefan (S); Sudhof, Thomas C (TC);

Affiliation: The Center for Basic Neuroscience, Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Grants: R37-MH52804-06 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2002-Jun; vol 22 (issue 11) : pp 4264-73

Dates: Created 2002/05/31; Completed 2002/07/05; Revised 2008/06/18;

PMID: 12040031, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adaptor Proteins, Signal Transducing Animals Binding Sites - physiology Binding, Competitive - physiology Calcium-Calmodulin-Dependent Protein Kinases Carrier Proteins - genetics; metabolism Cloning, Molecular Guanylate Kinase Humans Immunohistochemistry Macromolecular Substances Membrane Proteins Mice

Mice Molecular Sequence Data Nerve Tissue Proteins - genetics; metabolism Nucleoside-Phosphate Kinase - metabolism Organ Specificity Precipitin Tests Protein Binding - physiology Protein Isoforms - genetics; metabolism Protein Structure, Tertiary - physiology RNA - biosynthesis Rats Recombinant Fusion Proteins - genetics; metabolism Sequence Homology, Amino Acid

Associated Chemicals: APBA1 protein, human (0) ; Adaptor Proteins, Signal Transducing (0) ; Apba1 protein, mouse (0) ; Apba1 protein, rat (0) ; CASKIN2 protein, human (0) ; Carrier Proteins (0) ; Caskin1 protein, rat (0) ; Caskin2 protein, mouse (0) ; Macromolecular Substances (0) ; Membrane Proteins (0) ; Nerve Tissue Proteins (0) ; Protein Isoforms (0) ; Recombinant Fusion Proteins (0) ; caskin 2 protein, rat (0) ; RNA (63231-63-0) ; Calcium-Calmodulin-Dependent Protein Kinases (EC 2.7.11.17) ; CASK kinases (EC 2.7.4.-) ; Nucleoside-Phosphate Kinase (EC 2.7.4.4) ; Guanylate Kinase (EC 2.7.4.8)

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