Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Tosello-Trampont, A C; Kinchen, J M; Brugnera, E; Haney, L B; Hengartner, M O; Ravichandran, K S (2007). Identification of two signaling submodules within the CrkII/ELMO/Dock180 pathway regulating engulfment of apoptotic cells. Cell Death and Differentiation, 14(5):963-972.

Full text not available from this repository.

Abstract

Removal of apoptotic cells is a dynamic process coordinated by ligands on apoptotic cells, and receptors and other signaling proteins on the phagocyte. One of the fundamental challenges is to understand how different phagocyte proteins form specific and functional complexes to orchestrate the recognition/removal of apoptotic cells. One evolutionarily conserved pathway involves the proteins cell death abnormal (CED)-2/chicken tumor virus no. 10 (CT10) regulator of kinase (Crk)II, CED-5/180 kDa protein downstream of chicken tumor virus no. 10 (Crk) (Dock180), CED-12/engulfment and migration (ELMO) and MIG-2/RhoG, leading to activation of the small GTPase CED-10/Rac and cytoskeletal remodeling to promote corpse uptake. Although the role of ELMO : Dock180 in regulating Rac activation has been well defined, the function of CED-2/CrkII in this complex is less well understood. Here, using functional studies in cell lines, we observe that a direct interaction between CrkII and Dock180 is not required for efficient removal of apoptotic cells. Similarly, mutants of CED-5 lacking the CED-2 interaction motifs could rescue engulfment and migration defects in CED-5 deficient worms. Mutants of CrkII and Dock180 that could not biochemically interact could colocalize in membrane ruffles. Finally, we identify MIG-2/RhoG (which functions upstream of Dock180 : ELMO) as a possible point of crosstalk between these two signaling modules. Taken together, these data suggest that Dock180/ELMO and CrkII act as two evolutionarily conserved signaling submodules that coordinately regulate engulfment.

Item Type:Journal Article, refereed
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
DDC:570 Life sciences; biology
Language:English
Date:2007
Deposited On:11 Feb 2008 12:20
Last Modified:27 Nov 2013 18:45
Publisher:Nature Publishing Group
ISSN:1350-9047
Publisher DOI:10.1038/sj.cdd.4402094
Related URLs:http://www.nature.com/cdd/journal/v14/n5/abs/4402094a.html
PubMed ID:17304244
Citations:Web of Science®. Times Cited: 29
Google Scholar™

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page