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Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2.

Abstract : There are several endocytic pathways, which are either dependent on or independent of clathrin. This study focuses on a poorly characterized mechanism-clathrin- and caveolae-independent endocytosis-used by the interleukin-2 receptor beta (IL-2R beta). We address the question of its regulation in comparison with the clathrin-dependent pathway. First, we show that Ras-related C3 botulinum toxin substrate 1 (Rac1) is specifically required for IL-2R beta entry, and we identify p21-activated kinases (Paks) as downstream targets. By RNA interference, we show that Pak1 and Pak2 are both necessary for IL-2R beta uptake, in contrast to the clathrin-dependent route. We observe that cortactin, a partner of actin and dynamin-two essential endocytic factors-is required for IL-2R beta uptake. Furthermore, we find that cortactin acts downstream from Paks, suggesting control of its function by these kinases. Thus, we describe a cascade composed of Rac1, Paks and cortactin specifically regulating IL-2R beta internalization. This study indicates Paks as the first specific regulators of the clathrin-independent endocytosis pathway.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00332556
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Submitted on : Tuesday, October 21, 2008 - 11:05:40 AM
Last modification on : Tuesday, June 2, 2020 - 4:26:09 PM

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Alexandre Grassart, Annick Dujeancourt, Paul B. Lazarow, Alice Dautry-Varsat, Nathalie Sauvonnet. Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2.. EMBO Reports, EMBO Press, 2008, 9 (4), pp.356-62. ⟨10.1038/embor.2008.28⟩. ⟨pasteur-00332556⟩

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