Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formation
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...
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PeerJ Inc.
2013-08-01
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| Online Access: | https://peerj.com/articles/131.pdf |
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| author | Lucia Mathis Sarah Wernimont Sarah Affentranger Anna Huttenlocher Verena Niggli |
| author_facet | Lucia Mathis Sarah Wernimont Sarah Affentranger Anna Huttenlocher Verena Niggli |
| author_sort | Lucia Mathis |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:48:35Z |
| publishDate | 2013-08-01 |
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| spelling | doaj.art-c2e52d57328c496eb7fee9bd74d83bec2023-12-03T10:32:40ZengPeerJ Inc.PeerJ2167-83592013-08-011e13110.7717/peerj.131131Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formationLucia Mathis0Sarah Wernimont1Sarah Affentranger2Anna Huttenlocher3Verena Niggli4Institute of Pathology, University of Bern, Bern, SwitzerlandDepartments of Medical Microbiology and Immunology and Pediatrics, University of Wisconsin, Madison, WI, United States of AmericaInstitute of Pathology, University of Bern, Bern, SwitzerlandDepartments of Medical Microbiology and Immunology and Pediatrics, University of Wisconsin, Madison, WI, United States of AmericaInstitute of Pathology, University of Bern, Bern, SwitzerlandWe 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.https://peerj.com/articles/131.pdfT cellPhosphatidylinositol-4-phosphate 5-kinase type I (PIPKI)γ90PIPKIγ87UropodFlotillin |
| spellingShingle | Lucia Mathis Sarah Wernimont Sarah Affentranger Anna Huttenlocher Verena Niggli Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formation PeerJ T cell Phosphatidylinositol-4-phosphate 5-kinase type I (PIPKI)γ90 PIPKIγ87 Uropod Flotillin |
| title | Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formation |
| title_full | Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formation |
| title_fullStr | Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formation |
| title_full_unstemmed | Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formation |
| title_short | Determinants of phosphatidylinositol-4-phosphate 5-kinase type Iγ90 uropod location in T-lymphocytes and its role in uropod formation |
| title_sort | determinants of phosphatidylinositol 4 phosphate 5 kinase type iγ90 uropod location in t lymphocytes and its role in uropod formation |
| topic | T cell Phosphatidylinositol-4-phosphate 5-kinase type I (PIPKI)γ90 PIPKIγ87 Uropod Flotillin |
| url | https://peerj.com/articles/131.pdf |
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