Formin INF2 regulates MAL-mediated transport of Lck to the plasma membrane of human T lymphocytes

  1. Andrés-Delgado, Laura 1
  2. Antón, Olga M. 1
  3. Madrid, Ricardo 1
  4. Byrne, Jennifer A. 2
  5. Alonso, Miguel A. 1
  1. 1 Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain; and
  2. 2 Children's Cancer Research Unit and the University of Sydney Department of Pediatrics and Child's Health, The Children's Hospital at Westmead, Westmead, Australia
Revista:
Blood

ISSN: 0006-4971,  1528-0020

Año de publicación: 2010

Volumen: 116

Número: 26

Páginas: 5919-5929

Tipo: Artículo

DOI: 10.1182/BLOOD-2010-08-300665 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Blood

Resumen

Expression of the src-family kinase lymphocyte-specific protein tyrosine kinase (Lck) at the plasma membrane is essential for it to fulfill its pivotal role in signal transduction in T lymphocytes. MAL, an integral membrane protein expressed in specific types of lymphoma, has been shown to play an important role in targeting Lck to the plasma membrane. Here we report that MAL interacts with Inverted Formin2 (INF2), a formin with the atypical property of promoting not only actin polymerization but also its depolymerization. In Jurkat T cells, INF2 colocalizes with MAL at the cell periphery and pericentriolar endosomes and along microtubules. Videomicroscopic analysis revealed that the MAL+ vesicles transporting Lck to the plasma membrane move along microtubule tracks. Knockdown of INF2 greatly reduced the formation of MAL+ transport vesicles and the levels of Lck at the plasma membrane and impaired formation of a normal immunologic synapse. The actin polymerization and depolymerization activities of INF2 were both required for efficient Lck targeting. Cdc42 and Rac1, which bind to INF2, regulate Lck transport in both Jurkat and primary human T cells. Thus, INF2 collaborates with MAL in the formation of specific carriers for targeting Lck to the plasma membrane in a process regulated by Cdc42 and Rac1.

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