Syntrophin proteins as Santa Claus: role(s) in cell signal transduction
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Cellular and Molecular Life Sciences
REVIEW
Syntrophin proteins as Santa Claus: role(s) in cell signal transduction Hina F. Bhat · Marvin E. Adams · Firdous A. Khanday
Received: 11 August 2012 / Revised: 21 November 2012 / Accepted: 3 December 2012 / Published online: 21 December 2012 © Springer Basel 2012
Abstract Syntrophins are a family of cytoplasmic membrane-associated adaptor proteins, characterized by the presence of a unique domain organization comprised of a C-terminal syntrophin unique (SU) domain and an N-terminal pleckstrin homology (PH) domain that is split by insertion of a PDZ domain. Syntrophins have been recognized as an important component of many signaling events, and they seem to function more like the cell’s own personal ‘Santa Claus’ that serves to ‘gift’ various signaling complexes with precise proteins that they ‘wish for’, and at the same time care enough for the spatial, temporal control of these signaling events, maintaining overall smooth functioning and general happiness of the cell. Syntrophins not only associate various ion channels and signaling proteins to the dystrophin-associated protein complex (DAPC), via a direct interaction with dystrophin protein but also serve as a link between the extracellular matrix and the intracellular downstream targets and cell cytoskeleton by interacting with F-actin. They play an important role in regulating the postsynaptic signal transduction, sarcolemmal localization of nNOS, EphA4 signaling at the neuromuscular junction, and G-protein mediated signaling. In our previous work, we reported a differential expression pattern of alpha-1syntrophin (SNTA1) protein in esophageal and breast H. F. Bhat · F. A. Khanday (*) Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir 190006, India e-mail: [email protected] H. F. Bhat e-mail: [email protected] M. E. Adams Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA e-mail: [email protected]
carcinomas. Implicated in several other pathologies, like cardiac dys-functioning, muscular dystrophies, diabetes, etc., these proteins provide a lot of scope for further studies. The present review focuses on the role of syntrophins in membrane targeting and regulation of cellular proteins, while highlighting their relevance in possible development and/or progression of pathologies including cancer which we have recently demonstrated. Keywords Adaptor proteins · Syntrophins · Santa Claus · Signal transduction · Protein targeting
Introduction Cell signaling is a very complex system of cell communication that governs and coordinates the basic activities of a cell and coordinates its varied cellular actions. The ability of a cell to perceive and correctly respond to its microenvironment is the basis of its development and normal tissue homeostasis. Despite the multiple studies carried out all over the world, it is still unclear how exactly cells regulate the mechanisms that control the cross-talk between signaling cascades and how specifici
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