QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online August 20, 2008
doi: 10.1242/10.1242/jcs.023911

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, C. Articles by Field, J. Search for Related Content PubMed PubMed Citation Articles by Wang, C. Articles by Field, J. Social Bookmarking                         What's this?

Mitochondrial shuttling of CAP1 promotes actin- and cofilin-dependent apoptosis

Changhui Wang^1,*,, Guo-Lei Zhou^1,*,, Srilakshmi Vedantam¹, Peng Li² and Jeffrey Field^1,

¹ Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
² Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China

Authors for correspondence (e-mails: guozhou{at}upenn.edu; jfield{at}upenn.edu)

Accepted 5 June 2008

Mitochondria play a central role in regulating apoptosis by releasing proapoptotic contents such as cytochrome c, and generating reactive oxygen species (ROS). Early in apoptosis, proteins translocate to mitochondria to promote the release of their contents. Here, we show that the actin- and cofilin-interacting protein CAP1 has a role in apoptosis. When we induced apoptosis, CAP1 rapidly translocated to the mitochondria independently of caspase activation. Translocation was proapoptotic because CAP1-knockdown cells were resistant to apoptosis inducers. Overexpression of wild-type CAP1 did not stimulate apoptosis on its own, but stimulated cofilin-induced apoptosis. Apoptosis induction required a mitochondrial-targeting domain, localized in the N-terminus and also the actin-binding domain in the C-terminus. Taken together, these studies suggest that CAP1 provides a direct link from the actin cytoskeleton to the mitochondria by functioning as an actin shuttle.

Key words: Cyclase-associated protein, Srv2, ASP-56, Reactive oxygen species, Cytochrome c, Staurosporine, Etoposide

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. Wakeel, J. A. Kuriakose, and J. W. McBride An Ehrlichia chaffeensis Tandem Repeat Protein Interacts with Multiple Host Targets Involved in Cell Signaling, Transcriptional Regulation, and Vesicle Trafficking Infect. Immun., May 1, 2009; 77(5): 1734 - 1745. [Abstract] [Full Text] [PDF]