RRC ID 11677
Author Padash-Barmchi M, Browne K, Sturgeon K, Jusiak B, Auld VJ.
Title Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia.
Journal J. Cell. Sci.
Abstract The tricellular junction (TCJ) forms at the convergence of bicellular junctions from three adjacent cells in polarized epithelia and is necessary for maintaining the transepithelial barrier. In the fruitfly Drosophila, the TCJ is generated at the meeting point of bicellular septate junctions. Gliotactin was the first identified component of the TCJ and is necessary for TCJ and septate junction development. Gliotactin is a member of the neuroligin family and associates with the PDZ protein discs large. Beyond this interaction, little is known about the mechanisms underlying Gliotactin localization and function at the TCJ. In this study, we show that Gliotactin is phosphorylated at conserved tyrosine residues, a process necessary for endocytosis and targeting to late endosomes and lysosomes for degradation. Regulation of Gliotactin levels through phosphorylation and endocytosis is necessary as overexpression results in displacement of Gliotactin away from the TCJ throughout the septate junction domain. Excessive Gliotactin in polarized epithelia leads to delamination, paired with subsequent migration, and apoptosis. The apoptosis and the resulting compensatory proliferation resulting from high levels of Gliotactin are mediated by the Drosophila JNK pathway. Therefore, Gliotactin levels within the cell membrane are regulated to ensure correct protein localization and cell survival.
Volume 123(Pt 23)
Pages 4052-62
Published 2010-12-1
DOI 10.1242/jcs.066605
PII jcs.066605
PMID 21045109
MeSH Amino Acid Motifs Animals Cell Polarity* Cell Proliferation Cell Survival Drosophila / chemistry Drosophila / cytology Drosophila / genetics Drosophila / metabolism* Endocytosis* Endosomes / genetics Endosomes / metabolism Epithelial Cells / chemistry Epithelial Cells / cytology Epithelial Cells / metabolism* Intercellular Junctions / chemistry Intercellular Junctions / metabolism* Membrane Proteins / chemistry Membrane Proteins / genetics Membrane Proteins / metabolism* Nerve Tissue Proteins / chemistry Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Phosphorylation Protein Transport
IF 4.517
Times Cited 9
Drosophila UAS-Bsk DN