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The neuronal protein Kidins220/ARMS associates with ICAM-3 and other uropod components and regulates T-cell motility

AuthorsMartín Jean-Mairet, Roberto; López-Menéndez, Celia ; Sánchez-Ruiloba, Lucía; Sacristán, Sandra; Rodríguez-Martínez, María ; Riol-Blanco, Lorena; Rodríguez-Fernández, José Luis ; Campanero, Miguel R. ; Iglesias, Teresa
Cell migration
T cells
Issue DateApr-2011
CitationEuropean Journal of Immunology 41(4): 1035-1046 (2011)
AbstractKinase D interacting substrate of 220kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is a protein that is mainly expressed in brain and neural cells where its function is only starting to be characterized. Here, we show that Kidins220/ARMS is also expressed in T lymphocytes where it is highly concentrated at the uropod of polarized T cells. In this cellular model, Kidins220/ARMS colocalizes with typical uropod T-cell molecules and coimmunoprecipitates with ICAM-3. Furthermore, Kidins220/ARMS associates with raft domains at the uropod and coimmunoprecipitates with caveolin-1, a molecule we show here to be also expressed in T cells. Importantly, induction of morphological polarization in primary T lymphocytes and Jurkat cells enhances Kidins220/ARMS colocalization with ICAM-3. Conversely, disruption of cell polarity provokes Kidins220/ARMS redistribution from the uropod to other cellular regions and drastically impairs its association with ICAM-3 in a protein kinase C-dependent manner. Finally, Kidins220/ARMS knockdown in human polarized T-cell lines promotes both basal and stromal cell-derived factor-1α-induced directed migration, identifying a novel function for this molecule. Altogether, our findings show that Kidins220/ARMS is a novel component of the uropod involved in the regulation of T-cell motility, an essential process for the immune response.
Description12 páginas, 7 figuras.-- et al.
Publisher version (URL)http:dx.doi.org/10.1002/eji.201040513
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