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

12 páginas, 7 figuras.-- et al.Kinase 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.This work was supported by grants PI021058 to J. L. R. F., SAF2007-60647 to M. R. C., and PI020704, SAF2008-01951 from “Ministerio de Ciencia e Innovación,” CAM S-SAL-0202-2006-01 from “Comunidad de Madrid” and CIBERNED from “Instituto de Salud Carlos III” to T. I. R. M. J. was supported by a fellowship “Formación de Profesorado Universitario” (FPU) and an I3P fellowship from BIOTOOLS SA (Spain) and the CSIC. C. L. M. was recipient of a fellowship “Formación de Profesorado Universitario” (FPU) and now is recipient of a research contract funded by “Comunidad de Madrid” (Spain).Peer reviewe