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The role of myotubularin in cellular morphogenesis

Abstract

Cellular morphogenesis is an important process crucial for the proper function of nearly all cells. Cell shape change is a dynamic and highly regulated process and requires the strict spatial control of numerous cellular processes including cytoskeletal remodeling and membrane trafficking. Phosphoinositide phosphates (PIPs) provide one means of spatiotemporally regulating specific cell morphogenesis-related processes through their recruitment of specific PIP-binding effector proteins. One PIP regulator, myotubularin \[a predicted PI(3)P and PI(3,5)P₂ phosphatase\] was identified as a gene essential for the ecdysone hormone-induced cellular elongation of Kc cells. To gain a better understanding of the in vivo mechanisms through which mtm-dependent phosphoinositide regulation provides the spatial information necessary for the proper execution of morphogenetic programs, the role of mtm in the morphogenesis of the Drosophila blood cells (hemocytes) was investigated. In this report, I verify previous in vitro studies in our lab implicating mtm in protrusion formation and proper endolysosomal membrane homeostasis, in vivo. Using Drosophila hemocytes, I also examine the relationship between mtm-dependent processes to cellular morphogenesis. Our work points toward a model in which mtm, through the strict spatiotemporal regulation of class II PI 3-kinase (Pi3K68D)-synthesized PI(3)P pools, regulates the recruitment and activity of specific PIP binding effector proteins such as Spir to then mediate specific cellular events such as cytoskeletal remodeling and endolysosomal membrane trafficking to control cellular morphogenesis. This study therefore provides greater insight into the mechanisms through which phosphoinositides regulate and integrate multiple cellular processes to mediate changes in cell shape.

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