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

Authors: Grassart, Alexandre; Dujeancourt, Annick; Lazarow, Paul B.; Dautry-Varsat, Alice; Sauvonnet, Nathalie;

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 β (IL‐2Rβ). 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‐2Rβ 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‐2Rβ 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‐2Rβ 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‐2Rβ internalization. This study indicates Paks as the first specific regulators of the clathrin‐independent endocytosis pathway.

Keywords

rac1 GTP-Binding Protein, Microscopy, Fluorescence, p21-Activated Kinases, Humans, RNA Interference, Receptors, Interleukin-2, Cortactin, Clathrin, Endocytosis, Cell Line

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
99
Top 10%
Top 10%
Top 10%
gold