| First Author | Mathis L | Year | 2013 |
| Journal | PeerJ | Volume | 1 |
| Pages | e131 | PubMed ID | 24010013 |
| Mgi Jnum | J:201155 | Mgi Id | MGI:5511093 |
| Doi | 10.7717/peerj.131 | Citation | Mathis L, et al. (2013) Determinants of phosphatidylinositol-4-phosphate 5-kinase type Igamma90 uropod location in T-lymphocytes and its role in uropod formation. PeerJ 1:e131 |
| abstractText | We have previously identified phosphatidylinositol-4-phosphate 5-kinase type I (PIPKI)gamma90 as a T cell uropod component. However, the molecular determinants and functional consequences of its localization remain unknown. In this report, we seek to better understand the mechanisms involved in PIPKIgamma90 uropod targeting and the role that PIPKIgamma90 plays in T cell uropod formation. During T cell activation, PIPKIgamma90 cocaps with the membrane microdomain-associated proteins flotillin-1 and -2 and accumulates in the uropod. We report that the C-terminal 26 amino acid extension of PIPKIgamma90 is required for its localization to the uropod. We further use T cells from PIPKIgamma90(-/-) mice and human T cells expressing a kinase-dead PIPKIgamma90 mutant to examine the role of PIPKIgamma90 in a T cell uropod formation. We find that PIPKIgamma90 deficient T cells have elongated uropods on ICAM-1. Moreover, in human T cells overexpression of PIPKIgamma87, a naturally occurring isoform lacking the last 26 amino acids, suppresses uropod formation and impairs capping of uropod proteins such as flotillins. Transfection of human T cells with a dominant-negative mutant of flotillin-2 in turn attenuates capping of PIPKIgamma90. Our data contribute to the understanding of the molecular mechanisms that regulate T cell uropod formation. |
