RT Journal Article T1 Formin INF2 regulates MAL-mediated transport of Lck to the plasma membrane of human T lymphocytes A1 Andrés-Delgado, Laura A1 Antón Hurtado, Olga María A1 Byrne, Jennifer A1 Alonso, Miguel A1 Madrid González, Ricardo AB 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. PB American Society of Hematology SN 0006-4971 YR 2010 FD 2010 LK https://hdl.handle.net/20.500.14352/96985 UL https://hdl.handle.net/20.500.14352/96985 LA eng NO Laura Andrés-Delgado, Olga M. Antón, Ricardo Madrid, Jennifer A. Byrne, Miguel A. Alonso; Formin INF2 regulates MAL-mediated transport of Lck to the plasma membrane of human T lymphocytes. Blood 2010; 116 (26): 5919–5929. doi: https://doi.org/10.1182/blood-2010-08-300665 NO Ministerio de Ciencia e Innovación (España) DS Docta Complutense RD 6 abr 2025