Extracellular Mipp1 Activity Confers Migratory Advantage to Epithelial Cells during Collective Migration
Extracellular Mipp1 Activity Confers Migratory Advantage to Epithelial Cells during Collective Migration
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DOI：
10.1016/j.celrep.2015.10.071
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发表时间：
2015-12-15
期刊：
影响因子：
8.8
通讯作者：
Andrew, Deborah J.
中科院分区：
文献类型：
--
作者：
Cheng, Yim Ling;Andrew, Deborah J.
多重肌醇多聚磷酸酶(MIPP)是一种高度保守但知之甚少的组氨酸磷酸酶，它能将高阶IP(IP4-IP6)去磷酸化成IP3。为了深入了解这些酶的生物学作用，我们对果蝇mipp1进行了表征。Mipp1在胚胎气管中动态表达，特别是在晚期迁移分支的主导细胞中，其定位于质膜和丝状伪足。成纤维细胞生长因子信号激活这些细胞中mipp1的表达，在这些细胞中形成广泛的丝状足细胞，通过细胞嵌入来驱动迁移和延伸。我们发现，Mipp1通过其胞外活性促进了引导细胞中丝状足细胞的形成和/或稳定。Mipp1的缺失减少了丝足的数量，而mipp1的过表达则以一种磷酸酶活性依赖的方式增加了丝足的数量。重要的是，Mipp1的表达使细胞在伸长的气管分支中处于领先地位。综上所述，这些发现表明，细胞外的肌醇多磷酸盐池影响细胞发育过程中的行为。
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.