Procaspase-3 regulates fibronectin secretion and influences adhesion, migration and survival independently of catalytic function

• Type of Material: Article
• Authors: Matthew Brentnall, Emory University; David B. Weir, Emory University; Anthony Rongvaux, Yale University; Adam Marcus, Emory University; Lawrence Boise, Emory University
• Language: English
• Date: 2014-05-15
• Publisher: Company of Biologists
• Publication Version: Final Published Version
• Copyright Statement: © 2014. Published by The Company of Biologists Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1242/jcs.135137
• Title of Journal or Parent Work: Journal of Cell Science
• ISSN: 0021-9533
• Volume: 127
• Issue: 10
• Start Page: 2217
• End Page: 2226
• Grant/Funding Information: The work was funded by the National Institutes of Health [grant number R01 CA127910 to L.H.B.].; Additional support was provided by the Georgia Research Alliance and the TJ Martell Foundation (to L.H.B.).
• Keywords: ACTIVATION; Cell Biology; APOPTOSIS; Life Sciences & Biomedicine; CELL-MIGRATION; Adhesion; FIBROBLASTS; DIFFERENTIATION; ACTIN; Migration; DISTINCT ROLES; Caspase; DEATH; REGENERATION; Science & Technology; INHIBITION
• Research Categories: Biology, Cell

Abstract

Caspase-3 is an effector caspase that is activated downstream of mitochondrial outer-membrane permeabilization (MOMP) during apoptosis. However, previous work has demonstrated that caspase- 3-deficient mouse embryonic fibroblasts (MEFs) are resistant to mitochondrially mediated cell death and display a delay in the mitochondrial events of apoptosis, including Bax activation, MOMP and release of cytochrome c. Here, we show that caspase-3 regulates fibronectin secretion and impacts on cell morphology, adhesion and migration. Surprisingly, the catalytic activity of caspase-3 is not required for these non-apoptotic functions. Moreover, we found that caspase-3-deficient MEFs are not resistant to death by anoikis and that exogenous fibronectin protects wild-type MEFs from cell death induced by serum withdrawal. Taken together, our data indicate that procaspase-3 has a non-apoptotic function; it regulates the secretion of fibronectin and influences morphology, adhesion and migration. Furthermore, this novel procaspase-3 function might alter the apoptotic threshold of the cell.