Determinants of phosphatidylinositol-4-phosphate 5-kinase type I gamma 90 uropod location in T-lymphocytes and its role in uropod formation

作者：Mathis Lucia; Wernimont Sarah; Affentranger Sarah; Huttenlocher Anna; Niggli Verena^*

来源：PeerJ, 2013, 1: UNSP e131.

DOI：10.7717/peerj.131

• T cell
• Phosphatidylinositol-4-phosphate 5-kinase type I (PIPKI)gamma 90
• PIPKI gamma 87
• Uropod
• Flotillin

We have previously identified phosphatidylinositol-4-phosphate 5-kinase type I (PIPKI)gamma 90 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 PIPKI gamma 90 uropod targeting and the role that PIPKI gamma 90 plays in T cell uropod formation. During T cell activation, PIPKI gamma 90 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 PIPKI gamma 90 is required for its localization to the uropod. We further use T cells from PIPKI gamma 90(-/-) mice and human T cells expressing a kinase-dead PIPKI gamma 90 mutant to examine the role of PIPKI gamma 90 in a T cell uropod formation. We find that PIPKI gamma 90 deficient T cells have elongated uropods on ICAM-1. Moreover, in human T cells overexpression of PIPKI gamma 87, 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 PIPKI gamma 90. Our data contribute to the understanding of the molecular mechanisms that regulate T cell uropod formation.

• 出版日期2013-8-29