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Matricellular Signal Transduction Involving Calmodulin in the Social Amoebozoan Dictyostelium
Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road North, Mississauga, ON, L5L 1C6, Canada
Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON, M5S 3G5, Canada
Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Richard B. Simches Research Center, 185 Cambridge Street, Boston, MA 02114, USA
* Author to whom correspondence should be addressed.
Received: 27 December 2012; in revised form: 24 January 2013 / Accepted: 5 February 2013 / Published: 15 February 2013
Abstract: The social amoebozoan Dictyostelium discoideum undergoes a developmental sequence wherein an extracellular matrix (ECM) sheath surrounds a group of differentiating cells. This sheath is comprised of proteins and carbohydrates, like the ECM of mammalian tissues. One of the characterized ECM proteins is the cysteine-rich, EGF-like (EGFL) repeat-containing, calmodulin (CaM)-binding protein (CaMBP) CyrA. The first EGFL repeat of CyrA increases the rate of random cell motility and cyclic AMP-mediated chemotaxis. Processing of full-length CyrA (~63 kDa) releases two major EGFL repeat-containing fragments (~45 kDa and ~40 kDa) in an event that is developmentally regulated. Evidence for an EGFL repeat receptor also exists and downstream intracellular signaling pathways involving CaM, Ras, protein kinase A and vinculin B phosphorylation have been characterized. In total, these results identify CyrA as a true matricellular protein comparable in function to tenascin C and other matricellular proteins from mammalian cells. Insight into the regulation and processing of CyrA has also been revealed. CyrA is the first identified extracellular CaMBP in this eukaryotic microbe. In keeping with this, extracellular CaM (extCaM) has been shown to be present in the ECM sheath where it binds to CyrA and inhibits its cleavage to release the 45 kDa and 40 kDa EGFL repeat-containing fragments. The presence of extCaM and its role in regulating a matricellular protein during morphogenesis extends our understanding of CaM-mediated signal transduction in eukaryotes.
Keywords: matricellular; signal transduction; EGF-like repeats; extracellular matrix; calmodulin; morphogenesis; cell differentiation; development
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O'Day, D.H.; Huber, R.J. Matricellular Signal Transduction Involving Calmodulin in the Social Amoebozoan Dictyostelium. Genes 2013, 4, 33-45.
O'Day DH, Huber RJ. Matricellular Signal Transduction Involving Calmodulin in the Social Amoebozoan Dictyostelium. Genes. 2013; 4(1):33-45.
O'Day, Danton H.; Huber, Robert J. 2013. "Matricellular Signal Transduction Involving Calmodulin in the Social Amoebozoan Dictyostelium." Genes 4, no. 1: 33-45.