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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-47980

Neukomm, L J; Nicot, A S; Kinchen, J M; Almendinger, J; Pinto, S M; Zeng, S; Doukoumetzidis, K; Tronchère, H; Payrastre, B; Laporte, J F; Hengartner, M O (2011). The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5-CED-12 in C. elegans. Development, 138(10):2003-2014.

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Abstract

Multicellular organisms use programmed cell death to eliminate unwanted or potentially harmful cells. Improper cell corpse removal can lead to autoimmune diseases. The development of interventional therapies that increase engulfment activity could represent an attractive approach to treat such diseases. Here, we describe mtm-1, the Caenorhabditis elegans homolog of human myotubularin 1, as a potential negative regulator of apoptotic cell corpse clearance. Loss of mtm-1 function leads to substantially reduced numbers of persistent cell corpses in engulfment mutants, which is a result of a restoration of engulfment function rather than of impaired or delayed programmed cell death. Epistatic analyses place mtm-1 upstream of the ternary GEF complex, which consists of ced-2, ced-5 and ced-12, and parallel to mig-2. Over-activation of engulfment results in the removal of viable cells that have been brought to the verge of death under limiting caspase activity. In addition, mtm-1 also promotes phagosome maturation in the hermaphrodite gonad, potentially through CED-1 receptor recycling. Finally, we show that the CED-12 PH domain can bind to PtdIns(3,5)P(2) (one target of MTM-1 phosphatase activity), suggesting that MTM-1 might regulate CED-12 recruitment to the plasma membrane.

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
DDC:570 Life sciences; biology
Language:English
Date:2011
Deposited On:03 May 2011 14:19
Last Modified:27 Nov 2013 19:04
Publisher:Company of Biologists
ISSN:0950-1991
Publisher DOI:10.1242/dev.060012
PubMed ID:21490059
Citations:Web of Science®. Times Cited: 11
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Scopus®. Citation Count: 13

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