The myotubularin phosphatase MTMR4 regulates sorting from early endosomes

Naughtin, MJ, Sheffield, DA, Rahman, P, Hughes, WE, Gurung, R, Stow, JL, Nandurkar, HH, Dyson, JM and Mitchell, CA (2010) The myotubularin phosphatase MTMR4 regulates sorting from early endosomes. Journal of Cell Science, 123 18: 3071-3083. doi:10.1242/jcs.060103

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Author Naughtin, MJ
Sheffield, DA
Rahman, P
Hughes, WE
Gurung, R
Stow, JL
Nandurkar, HH
Dyson, JM
Mitchell, CA
Title The myotubularin phosphatase MTMR4 regulates sorting from early endosomes
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 0021-9533
1477-9137
0269-3518
Publication date 2010-09-15
Sub-type Article (original research)
DOI 10.1242/jcs.060103
Open Access Status File (Publisher version)
Volume 123
Issue 18
Start page 3071
End page 3083
Total pages 13
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Collection year 2011
Language eng
Formatted abstract
Phosphatidylinositol 3-phosphate [PtdIns(3)P] regulates endocytic trafficking and the sorting of receptors through early endosomes, including the rapid recycling of transferrin (Tfn). However, the phosphoinositide phosphatase that selectively opposes this function is unknown. The myotubularins are a family of eight catalytically active and six inactive enzymes that hydrolyse PtdIns(3)P to form PtdIns. However, the role each myotubularin family member plays in regulating endosomal PtdIns(3)P and thereby endocytic trafficking is not well established. Here, we identify the myotubularin family member MTMR4, which localizes to early endosomes and also to Rab11- and Sec15-positive recycling endosomes. In cells with MTMR4 knockdown, or following expression of the catalytically inactive MTMR4, MTMR4C407A, the number of PtdIns(3)P-decorated endosomes significantly increased. MTMR4 overexpression delayed the exit of Tfn from early endosomes and its recycling to the plasma membrane. By contrast, expression of MTMR4C407A, which acts as a dominant-negative construct, significantly accelerated Tfn recycling. However, in MTMR4 knockdown cells Tfn recycling was unchanged, suggesting that other MTMs might also contribute to recycling. MTMR4 regulated the subcellular distribution of Rab11 and, in cells with RNAi-mediated knockdown of MTMR4, Rab11 was directed away from the pericentriolar recycling compartment. The subcellular distribution of VAMP3, a v-SNARE protein that resides in recycling endosomes and endosome-derived transport vesicles, was also regulated by MTMR4. Therefore, MTMR4 localizes at the interface of early and recycling endosomes to regulate trafficking through this pathway.
Keyword MTMR4
Myotubularin
Recycling endosomes
Tfn
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 26 Sep 2010, 00:04:07 EST