The Bro1 domain-containing Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration

Abstract

SummaryProtein tyrosine phosphatases (PTPs) are a group of tightly regulated enzymes that coordinate with protein tyrosine kinases to control protein phosphorylation during various cellular processes. Using genetic analysis in Drosophila non-transmembrane PTPs, we identified one role that Myopic (Mop), the Drosophila homolog of the human His domain phosphotyrosine phosphatase (HDPTP), plays in cell adhesion. Depletion of Mop results in aberrant integrin distribution and border cell dissociation during Drosophila oogenesis. Interestingly, Mop phosphatase activity is not required for its role in maintaining border cell cluster integrity. We further identified Rab4 GTPase as a Mop interactor in a yeast two-hybrid screen. Expression of the Rab4 dominant-negative mutant leads to border cell dissociation and suppression of Mop-induced wingblade adhesion defects, suggesting a critical role of Rab4 in Mop-mediated signaling. In mammals, it has been shown that Rab4-dependent recycling of integrins is necessary for cell adhesion and migration. We found that human HDPTP regulates the spatial distribution of Rab4 and integrin trafficking. Depletion of HDPTP resulted in actin reorganization and increased cell motility. Together, our findings suggest an evolutionarily conserved function of HDPTP-Rab4 in the regulation of endocytic trafficking, cell adhesion and migration.

An RNAi Screen To Identify Protein Phosphatases That Function Within theDrosophilaCircadian Clock

“…It functions in many cellular processes including phagocytosis, neurogenesis, and cell migration (Stroschein-Stevenson et al 2006; Chen et al 2012). We tested the available Ptpmeg2 P element transposon insert lines and clock cell-specific Ptpmeg2 overexpression flies, but none of these genetic reagents altered activity rhythms (Table 2).…”

EGFR controls Drosophila tracheal tube elongation by intracellular trafficking regulation

“…In addition, EGFR can phosphorylate Clathrin in a Src-mediated mechanism regulating its redistribution [53], can also phosphorylate the endocytic adaptor protein Eps15 [54,55], and can induce E-Cadh macropinocytosis [56]. Interestingly, myopic was shown to regulate EGFR signalling [57] and to interact with Rab4 [58]. Furthermore, Rac1, which can be a target of Receptor Tyrosine Kinases [59], has been shown to regulate Serp and Crb in the trachea [60].…”

A Drosophila‐centric view of protein tyrosine phosphatases

“…Out of 73 PTPN23 orthologs examined, all but 6 harbor a conserved serine residue (VHCS S GXG) instead of an alanine residue (VHCS A GXG) in the PTP signature motif; it has been suggested that this Ala to Ser mutation in PTPN23 may influence the entry and positioning of the substrate in the catalytic pocket [99]. Besides, the D → K mutation in the WPD loop appears to contribute to Mop 's lack of observed catalytic activity [100]. Despite the abrogation of its catalytic activity, Mop has been reported to act as a tumor suppressor by influencing different signaling pathways, for example through the inhibition of receptor protein kinase signaling during their endocytic internalization [101], and by interacting and regulating the transcription factor Yorkie [102].…”