Abstract
We identify a complex of three proteins in brain that has the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. The three proteins are: (1) CASK, a protein related to MAGUKs (membrane-associated guanylate kinases); (2) Mint1, a putative vesicular trafficking protein; and (3) Veli1, -2, and -3, vertebrate homologs of C. elegans LIN-7. CASK, Mint1, and Velis form a tight, salt-resistant complex that can be readily isolated. CASK, Mint1, and Velis contain PDZ domains in addition to other modules. However, no PDZ domains are involved in complex formation, leaving them free to recruit cell adhesion molecules, receptors, and channels to the complex. We propose that the tripartite complex acts as a nucleation site for the assembly of proteins involved in synaptic vesicle exocytosis and synaptic junctions.
MeSH Terms
Adaptor Proteins, Signal Transducing
Animals
Brain Chemistry/physiology
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Calcium-Binding Proteins
Calcium-Calmodulin-Dependent Protein Kinases
Carrier Proteins/analysis,genetics,metabolism
Cell Adhesion/physiology
Cell Membrane/chemistry,metabolism
Cloning, Molecular
Exocytosis/physiology
Glycoproteins
Guanylate Kinases
Helminth Proteins/analysis,genetics,metabolism
Humans
Membrane Glycoproteins/analysis
Membrane Proteins/analysis,genetics,metabolism
Mice
Molecular Sequence Data
Nerve Tissue Proteins/analysis,genetics,metabolism
Neurons/chemistry,cytology,physiology
Neuropeptides
Nucleoside-Phosphate Kinase/analysis,genetics,metabolism
Protein Binding/physiology
Rats
Sequence Homology, Amino Acid
Synaptic Vesicles/chemistry,physiology
Synaptophysin/analysis
Synaptotagmins
Tumor Suppressor Proteins
Vesicular Transport Proteins
Chemicals
APBA1 protein, human
Adaptor Proteins, Signal Transducing
Apba1 protein, mouse
Apba1 protein, rat
Caenorhabditis elegans Proteins
Calcium-Binding Proteins
Carrier Proteins
Glycoproteins
Helminth Proteins
LIN-7 protein, C elegans
LIN7B protein, human
Lin7a protein, mouse
Lin7b protein, mouse
Lin7c protein, mouse
Membrane Glycoproteins
Membrane Proteins
Nerve Tissue Proteins
Neuropeptides
Synaptophysin
Tumor Suppressor Proteins
Vesicular Transport Proteins
neurexophilin
Synaptotagmins
neurexin Ibeta
CASK kinases
Calcium-Calmodulin-Dependent Protein Kinases
Nucleoside-Phosphate Kinase
DLG2 protein, human
Guanylate Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Butz S
Center for Basic Neuroscience, Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center at Dallas, 75235, USA.
Okamoto M
Südhof T C