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Extracellular Mipp1 Activity Confers Migratory Advantage to Epithelial Cells during Collective Migration
Yim Ling Cheng1, Deborah J Andrew1
1Department of Cell Biology, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
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.
Insights
Multiple inositol polyphosphate phosphatase (Mipp) dephosphorylates inositol phosphates. Drosophila Mipp1 facilitates filopodia formation and cell migration during embryonic development, suggesting extracellular inositol polyphosphates influence cell behavior.
Area of Science:
- Biochemistry
- Developmental Biology
- Cell Biology
Background:
- Multiple inositol polyphosphate phosphatase (Mipp) is a conserved histidine phosphatase.
- Mipp dephosphorylates higher-order inositol phosphates (IPs) to IP3.
- The biological roles of Mipp enzymes remain poorly understood.
Purpose of the Study:
- To characterize the function of Drosophila mipp1 in embryonic development.
- To investigate the role of Mipp1 in cell migration and filopodia formation.
- To explore the influence of extracellular inositol polyphosphates on cell behavior.
Main Methods:
- Characterization of Drosophila mipp1 expression patterns.
- Localization studies of Mipp1 in embryonic trachea.
- Analysis of filopodia formation and cell migration in response to Mipp1 manipulation (loss and overexpression).
- Investigation of FGF signaling pathway involvement.
Main Results:
- Mipp1 is dynamically expressed in embryonic tracheal leading cells during migration.
- Mipp1 localizes to the plasma membrane and filopodia.
- FGF signaling activates mipp1 expression, promoting filopodia formation and cell migration.
- Mipp1 facilitates filopodia formation/stabilization via extracellular activity.
- Mipp1 loss reduces filopodia; overexpression increases filopodia in a phosphatase-dependent manner.
- Mipp1 expression confers a migratory advantage to leading cells.
Conclusions:
- Extracellular Mipp1 plays a crucial role in regulating filopodia dynamics and cell migration during embryonic tracheal development.
- Mipp1 activity is regulated by FGF signaling.
- These findings highlight the importance of extracellular inositol polyphosphate metabolism in controlling cell behavior during development.
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