Cortactin and dynamin are required for the clathrin-independent endocytosis of gammac cytokine receptor.
Endocytosis is critical for many cellular functions. We show that endocytosis of the common gammac cytokine receptor is clathrin independent by using a dominant-negative mutant of Eps15 or RNA interference to knock down clathrin heavy chain. This pathway is synaptojanin independent and requires the GTPase dynamin. In addition, this process requires actin polymerization. To further characterize the function of dynamin in clathrin-independent endocytosis, in particular its connection with the actin cytoskeleton, we focused on dynamin-binding proteins that interact with F-actin. We compared the involvement of these proteins in the clathrin-dependent and -independent pathways. Thus, we observed that intersectin, syndapin, and mAbp1, which are necessary for the uptake of transferrin (Tf), a marker of the clathrin route, are not required for gammac receptor endocytosis. Strikingly, cortactin is needed for both gammac and Tf internalizations. These results reveal the ubiquitous action of cortactin in internalization processes and suggest its role as a linker between actin dynamics and clathrin-dependent and -independent endocytosis.
Sauvonnet
Nathalie
N
Unité de Biologie des Interactions Cellulaires, Institut Pasteur, Centre National de la Recherche Scientifique, URA 2582, 75724 Paris, Cedex 15, France.
Dujeancourt
Annick
A
Dautry-Varsat
Alice
A
D000199:Actins / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism*; D051356:Cortactin; D003599:Cytoskeleton / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
D000199:Actins; D033942:Adaptor Proteins, Vesicular Transport; C495868:CTTN protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002966:Clathrin; D051356:Cortactin; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D018121:Receptors, Cytokine; D011993:Recombinant Fusion Proteins; D014168:Transferrin; C115919:intersectin 1; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases; D034281:Dynamins