S100A10/p11: family, friends and functions
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S100A10, also known as p11 or annexin 2 light chain, is a member of the S100 family of small, dimeric EF hand-type Ca2+-binding proteins that generally modulate cellular target proteins in response to intracellular Ca2+ signals. In contrast to all other S100 proteins, S100A10 is Ca2+ insensitive because of amino acid replacements in its Ca2+-binding loops that lock the protein in a permanently active state. Within cells, the majority of S100A10 resides in a tight heterotetrameric complex with the peripheral membrane-binding protein annexin A2 that directs the complex to specific target membranes, in particular the plasma membrane and the membrane of early endosomes. Several other Ca2+-independent interaction partners of S100A10 have been described in the recent past. Many of these interactions, which have been shown to be of functional significance for the respective partner, involve plasma membrane-resident proteins. In most of these cases, S100A10, probably residing in a complex with annexin A2, appears to regulate the intracellular trafficking of the respective target protein and thus its functional expression at the cell surface. In this paper, we review the current information on S100A10 protein interactions placing a particular emphasis on data that contribute to an understanding of the mechanistic basis of the S100A10 action. Based on these data, we propose that S100A10 functions as a linker tethering certain transmembrane proteins to annexin A2 thereby assisting their traffic to the plasma membrane and/or their firm anchorage at certain membrane sites.
KeywordsCytosolic calcium TRP channels Transport Receptor Ion channel modulation
We thank J. Daut (University of Marburg) for comments on the manuscript and the Deutsche Forschungsgemeinschaft (DFG), the Interdisciplinary Centre for Clinical Research (IZKF) and the Innovative Medical Research (IMF) of the Münster Medical School for support.
- 13.Huang XL, Pawliczak R, Yao XL, Cowan MJ, Gladwin MT, Walter MJ, Holtzman MJ, Madara P, Logun C, Shelhamer JH (2003) Interferon-gamma induces p11 gene and protein expression in human epithelial cells through interferon-gamma-activated sequences in the p11 promoter. J Biol Chem 278:9298–9308PubMedCrossRefGoogle Scholar
- 24.Hayes MJ, Merrifield CJ, Shao D, Ayala-Sanmartin J, Schorey CD, Levine TP, Proust J, Curran J, Bailly M, Moss SE (2004) Annexin 2 binding to phosphatidylinositol 4,5-bisphosphate on endocytic vesicles is regulated by the stress response pathway. J Biol Chem 279:14157–14164PubMedCrossRefGoogle Scholar
- 33.Renigunta V, Yuan H, Zuzarte M, Rinne S, Koch A, Wischmeyer E, Schlichthorl G, Gao Y, Karschin A, Jacob R, Schwappach B, Daut J, Preisig-Muller R (2006) The retention factor p11 confers an endoplasmic reticulum-localization signal to the potassium channel TASK-1. Traffic 7:168–181PubMedCrossRefGoogle Scholar
- 47.Verma R, Cutler DJ, Holmans P, Knowles JA, Crowe RR, Scheftner WA, Weissman MM, Depaulo JR Jr, Levinson DF, Potash JB (2007) Investigating the role of p11 (S100A10) sequence variation in susceptibility to major depression. Am J Med Genet B Neuropsychiatr Genet (in press)Google Scholar