Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formation

Mathis, Lucia; Wernimont, Sarah; Affentranger, Sarah; Huttenlocher, Anna; Niggli, Verena (2013). Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formation. PeerJ, 1, e131. PeerJ, Ltd 10.7717/peerj.131

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We have previously identified phosphatidylinositol-4-phosphate 5-kinase type I (PIPKI)γ90 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 PIPKIγ90 uropod targeting and the role that PIPKIγ90 plays in T cell uropod formation. During T cell activation, PIPKIγ90 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 PIPKIγ90 is required for its localization to the uropod. We further use T cells from PIPKIγ90(-/-) mice and human T cells expressing a kinase-dead PIPKIγ90 mutant to examine the role of PIPKIγ90 in a T cell uropod formation. We find that PIPKIγ90 deficient T cells have elongated uropods on ICAM-1. Moreover, in human T cells overexpression of PIPKIγ87, 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 PIPKIγ90. Our data contribute to the understanding of the molecular mechanisms that regulate T cell uropod formation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Inflammatory Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Affentranger, Sarah and Niggli, Verena

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2167-8359

Publisher:

PeerJ, Ltd

Language:

English

Submitter:

Andrea Arnold

Date Deposited:

07 Apr 2014 10:21

Last Modified:

13 Dec 2014 14:12

Publisher DOI:

10.7717/peerj.131

PubMed ID:

24010013

Uncontrolled Keywords:

T cell, Phosphatidylinositol-4-phosphate 5-kinase type I .PIPKI/ 90, PIPKI 87, Uropod, Flotillin

BORIS DOI:

10.7892/boris.46054

URI:

https://boris.unibe.ch/id/eprint/46054

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