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

Kinase D interacting substrate of 220 kDa (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.