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The alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptor trafficking regulator "stargazin" is related to the claudin family of proteins by Its ability to mediate cell-cell adhesion.

TitleThe alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptor trafficking regulator "stargazin" is related to the claudin family of proteins by Its ability to mediate cell-cell adhesion.
Publication TypeJournal Article
Year of Publication2005
AuthorsPrice, Maureen G., Davis Caleb F., Deng Fang, and Burgess Daniel L.
JournalThe Journal of biological chemistry
Volume280
Issue20
Pagination19711-20
Date Published2005 May 20
ISSN0021-9258
KeywordsAmino Acid Sequence, Animals, Base Sequence, Calcium Channels, Cell Adhesion, Cell Line, DNA, Humans, L Cells (Cell Line), Membrane Proteins, Mice, Microscopy, Electron, Molecular Sequence Data, Multigene Family, Mutation, Neurons, Phylogeny, Receptors, AMPA, Recombinant Proteins, Sequence Homology, Amino Acid, Signal Transduction, Transfection
AbstractMutations in the Cacng2 gene encoding the neuronal transmembrane protein stargazin result in recessively inherited epilepsy and ataxia in "stargazer" mice. Functional studies suggest a dual role for stargazin, both as a modulatory gamma subunit for voltage-dependent calcium channels and as a regulator of post-synaptic membrane targeting for alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors. Co-immunoprecipitation experiments demonstrate that stargazin can bind proteins of either complex in vivo, but it remains unclear whether it can associate with both complexes simultaneously. Cacng2 is one of eight closely related genes (Cacng1-8) encoding proteins with four transmembrane segments, cytoplasmic termini, and molecular masses between 25 and 44 kDa. This group of Cacng genes constitutes only one branch of a larger monophyletic assembly dominated by over 20 genes encoding proteins known as claudins. Claudins regulate cell adhesion and paracellular permeability as fundamental components of non-neuronal tight junctions. Because stargazin is structurally similar to claudins, we hypothesized that it might also have retained claudin-like functions inherited from a common ancestor. Here, we report that expression of stargazin in mouse L-fibroblasts results in cell aggregation comparable with that produced by claudins, and present evidence that the interaction is heterotypic and calcium dependent. The data suggest that the cell adhesion function of stargazin preceded its current role in neurons as a regulator of either voltage-dependent calcium channels or AMPA receptors. We speculate these complexes may have co-opted the established presence of stargazin at sites of close cell-cell contact to facilitate their own evolving intercellular signaling functions.
DOI10.1074/jbc.M500623200
Alternate JournalJ. Biol. Chem.


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