RRC ID 57151
Author Samarasekera GDNG, Auld VJ.
Title C-terminal Src kinase (Csk) regulates the tricellular junction protein Gliotactin independent of Src.
Journal Mol Biol Cell
Abstract Tricellular junctions (TCJs) are uniquely placed permeability barriers formed at the corners of polarized epithelia where tight junctions in vertebrates or septate junctions (SJ) in invertebrates from three cells converge. Gliotactin is a Drosophila TCJ protein, and loss of Gliotactin results in SJ and TCJ breakdown and permeability barrier loss. When overexpressed, Gliotactin spreads away from the TCJs, resulting in disrupted epithelial architecture, including overproliferation, cell delamination, and migration. Gliotactin levels are tightly controlled at the mRNA level and at the protein level through endocytosis and degradation triggered by tyrosine phosphorylation. We identified C-terminal Src kinase (Csk) as a tyrosine kinase responsible for regulating Gliotactin endocytosis. Increased Csk suppresses the Gliotactin overexpression phenotypes by increasing endocytosis. Loss of Csk causes Gliotactin to spread away from the TCJ. Although Csk is known as a negative regulator of Src kinases, the effects of Csk on Gliotactin are independent of Src and likely occur through an adherens junction associated complex. Overall, we identified a new Src-independent role for Csk in the control of Gliotactin, a key tricellular junction protein.
Volume 29(2)
Pages 123-136
Published 2018-1-15
DOI 10.1091/mbc.E17-04-0251
PII mbc.E17-04-0251
PMID 29167383
PMC PMC5909926
MeSH Adherens Junctions / metabolism* Animals CSK Tyrosine-Protein Kinase Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism Endocytosis / genetics Membrane Proteins / genetics Membrane Proteins / metabolism* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Phosphorylation Tight Junctions / metabolism src-Family Kinases / genetics src-Family Kinases / metabolism*
IF 3.905
Times Cited 6