Extracellular Mipp1 Activity Confers Migratory Advantage to Epithelial Cells during Collective Migration

Yim Ling Cheng, Deborah J Andrew

Research output: Contribution to journalArticle

Abstract

Multiple inositol polyphosphate phosphatase (Mipp), a highly conserved but poorly understood histidine phosphatase, dephosphorylates higher-order IPs (IP4-IP6) to IP3. To gain insight into the biological roles of these enzymes, we have characterized Drosophila mipp1. mipp1 is dynamically expressed in the embryonic trachea, specifically in the leading cells of migrating branches at late stages, where Mipp1 localizes to the plasma membrane and filopodia. FGF signaling activates mipp1 expression in these cells, where extensive filopodia form to drive migration and elongation by cell intercalation. We show that Mipp1 facilitates formation and/or stabilization of filopodia in leading cells through its extracellular activity. mipp1 loss decreases filopodia number, whereas mipp1 overexpression increases filopodia number in a phosphatase-activity-dependent manner. Importantly, expression of Mipp1 gives cells a migratory advantage for the lead position in elongating tracheal branches. Altogether, these findings suggest that extracellular pools of inositol polyphosphates affect cell behavior during development. Mipps are highly conserved enzymes that convert inositol polyphosphates (IP6, IP5, and IP4) to IP3. Cheng and Andrew have demonstrated that Drosophila Mipp1 is highly expressed in cells of migrating branches of the developing trachea where it functions extracellularly to facilitate filopodia formation and confer migratory advantage.

Original languageEnglish (US)
JournalCell Reports
DOIs
Publication statusAccepted/In press - Mar 20 2015

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Keywords

  • Epithelial migration
  • Filopodia
  • Inositol polyphosphates
  • mipp
  • Trachea

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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