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PMID: 22648168 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Molecular biology of the cell ·Vol. 23 ·No. 14 ·2012-07-00 ·Pages 2723-40

Jean S, Cox S, Schmidt EJ, Robinson FL, Kiger A

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.

MeSH Terms
Animals Cell Membrane/metabolism Cells, Cultured Drosophila Drosophila Proteins/genetics,metabolism Endosomes/metabolism Guanine Nucleotide Exchange Factors/metabolism Macrophages/metabolism Phosphatidylinositol Phosphates/metabolism Protein Transport Protein Tyrosine Phosphatases, Non-Receptor/genetics,metabolism RNA Interference RNA, Small Interfering rab GTP-Binding Proteins/metabolism
Chemicals
Drosophila Proteins Guanine Nucleotide Exchange Factors Phosphatidylinositol Phosphates RNA, Small Interfering Sbf protein, Drosophila phosphatidylinositol 3-phosphate Protein Tyrosine Phosphatases, Non-Receptor SBF2 protein, human myotubularin Rab11 protein, Drosophila rab GTP-Binding Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Jean Steve
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0380, USA.
Cox Sarah
Schmidt Eric J
Robinson Fred L
Kiger Amy
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.E12-05-0375
Published
2012-07-00
Epub
2012-00-30
Pages
2723-40
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC3395661
Subset
IM
Grants
NINDS NIH HHS · P30 NS047101 · United States
NIGMS NIH HHS · R01 GM078176 · United States
External Links
PubMed source DOI: 10.1091/mbc.E12-05-0375 PMC Full Text View journal details
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