title: Extracellular Mipp1 Activity Confers Migratory Advantage to Epithelial Cells during Collective Migration.
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.
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Yim Ling
authors.initials: YL
authors.lastname: Cheng
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: dandrew@jhmi.edu.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Andrew
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D004847:Epithelial Cells / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010802:Phylogeny; D011487:Protein Conformation; D034741:RNA, Small Interfering; D014132:Trachea / Q000196:embryology*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D010744:Phosphoric Monoester Hydrolases; C064119:multiple inositol-polyphosphate phosphatase
keywords: epithelial migration; filopodia; inositol polyphosphates; mipp; trachea