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Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2.
Grassart A., Dujeancourt A., Lazarow P. B., Dautry-Varsat A., Sauvonnet N.
EMBO Reports 9, 4 (2008) 356-62 - http://hal-pasteur.archives-ouvertes.fr/pasteur-00332556
(18344974)
Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2.
Alexandre Grassart1, Annick Dujeancourt1, Paul B. Lazarow1, Alice Dautry-Varsat1, Nathalie Sauvonnet () 1
1 :  BIC - Biologie des Interactions Cellulaires
CNRS : URA2582 – Institut Pasteur de Paris
25-28 rue du Docteur Roux 75724 Paris cedex 15
France
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.
Anglais
1469-221X

Articles dans des revues avec comité de lecture
10.1038/embor.2008.28
EMBO reports (EMBO Rep)
Publisher Nature Publishing Group: EMBO
ISSN 1469-221X (eISSN : 1469-3178)
internationale
04/2008
9
4
356-62

Cell Line – Clathrin – Cortactin – Endocytosis – Humans – Microscopy – Fluorescence – RNA Interference – Receptors – Interleukin-2 – p21-Activated Kinases – rac1 GTP-Binding Protein
Action Concertée, Programme Dynamique et Réactivité des Assemblages Biologiques Action Concertée Biologie Cellulaire, Moléculaire et Structurale.