Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling

Steve Jean, Sarah Cox, Eric J. Schmidt, Fred Robinson, Amy Kiger

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control.

Original languageEnglish (US)
Pages (from-to)2723-2740
Number of pages18
JournalMolecular Biology of the Cell
Volume23
Issue number14
DOIs
StatePublished - Jul 15 2012

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GTP Phosphohydrolases
Class II Phosphatidylinositol 3-Kinases
Macrophages
rab GTP-Binding Proteins
Guanine Nucleotide Exchange Factors
Endosomes
Phosphatidylinositols
Drosophila
Lipids
Membranes
phosphatidylinositol 3-phosphate
myotubularin
Phosphoinositide Phosphatases

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling. / Jean, Steve; Cox, Sarah; Schmidt, Eric J.; Robinson, Fred; Kiger, Amy.

In: Molecular Biology of the Cell, Vol. 23, No. 14, 15.07.2012, p. 2723-2740.

Research output: Contribution to journalArticle

Jean, Steve ; Cox, Sarah ; Schmidt, Eric J. ; Robinson, Fred ; Kiger, Amy. / Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling. In: Molecular Biology of the Cell. 2012 ; Vol. 23, No. 14. pp. 2723-2740.
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