Roles of cortactin, an actin polymerization mediator, in cell endocytosis.
Cortactin, an actin-binding protein and a substrate of Src, is encoded by the EMS1 oncogene. Cortactin is known to activate Arp2/3 complex-mediated actin polymerization and interact with dynamin, a large GTPase and proline rich domain-containing protein. Transferrin endocytosis was significantly reduced in cells by knock-down of cortactin expression as well as in vivo introduction of cortactin immunoreagents. Cortactin-dynamin interaction displayed morphologically dynamic co-distribution with a change in the endocytosis level in cells treated with an actin depolymerization reagent, cytochalasin D. In an in vitro beads assay, a branched actin network was recruited onto dynamin-coated beads in a cortactin Src homology domain 3 (SH3)-dependent manner. In addition, cortactin was found to function in the late stage of clathrin coated vesicle formation. Taken together, cortactin is required for optimal clathrin mediated endocytosis in a dynamin directed manner.
Chen
Li
L
Department of Pathology, School of Medicine, Nantong University, Nantong 226001, China. usazhujianwei@yahoo.com.cn.
Wang
Zhi-Wei
ZW
Zhu
Jian-wei
JW
Zhan
Xi
X
D051377:Actin-Related Protein 2 / Q000737:chemistry / Q000378:metabolism; D051378:Actin-Related Protein 3 / Q000737:chemistry / Q000378:metabolism; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D003062:Codon / Q000235:genetics; D051356:Cortactin / Q000737:chemistry / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D004705:Endocytosis / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D015513:Oncogene Proteins / Q000235:genetics; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D018909:src Homology Domains
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; D003062:Codon; D051356:Cortactin; D008840:Microfilament Proteins; D015513:Oncogene Proteins; D011108:Polymers; D014168:Transferrin; D015638:Cytochalasin D; D020558:GTP Phosphohydrolases