Loss of myosin VI no insert isoform (NoI) induces a defect in clathrin-mediated endocytosis and leads to caveolar endocytosis of transferrin receptor.
Myosin VI is a motor protein that moves toward the minus end of actin filaments. It is involved in clathrin-mediated endocytosis and associates with clathrin-coated pits/vesicles at the plasma membrane. In this article the effect of the loss of myosin VI no insert isoform (NoI) on endocytosis in nonpolarized cells was examined. The absence of myosin VI in fibroblasts derived from the Snell's waltzer mouse (myosin VI knock-out) gives rise to defective clathrin-mediated endocytosis with shallow clathrin-coated pits and a strong reduction in the internalization of clathrin-coated vesicles. To compensate for this defect in clathrin-mediated endocytosis, plasma membrane receptors such as the transferrin receptor (TfR) are internalized by a caveola-dependent pathway. Moreover the clathrin adaptor protein, AP-2, necessary for TfR internalization, follows the receptor and relocalizes in caveolae in Snell's waltzer fibroblasts.
Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom. cp344@cam.ac.uk
Claudia
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Puri
D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D033962:Adaptor Protein Complex 2; D015820:Cadherins; C499091:Cdh23 protein, mouse; D002966:Clathrin; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; C089785:myosin VI; D018995:Myosin Heavy Chains