Involvement of a novel ADP-ribosylation factor GTPase-activating protein, SMAP, in membrane trafficking: implications in cancer cell biology.
The endocytosis of cell membrane proteins is initiated by the binding of activated Arf6, a member of Ras-related GTPases, to the PM. A GAP specific for Arf6 triggers the budding of endocytotic vesicles from the PM by inactivating GTP-bound Arf6. We recently identified the SMAP gene that encodes an ArfGAP and is involved in the endocytosis of TfnR and possibly E-cadherin. In this review, we summarize the process of intracellular membrane trafficking, highlighting the roles played by the SMAP gene. Progression of cancer to malignancy occurs in parallel with the disappearance of E-cadherin, a central component of the adherens junction in epithelial cells. Therefore, elucidation of the molecular mechanism of E-cadherin endocytosis should be one of the key elements in tumor cell biology.
Tanabe
Kenji
K
Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan.
Kon
Shunsuke
S
Natsume
Waka
W
Torii
Tetsuo
T
Watanabe
Toshio
T
Satake
Masanobu
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D021381:Protein Transport / Q000502:physiology*; D011990:Receptors, Transferrin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D003598:Cytoskeletal Proteins; C484407:KIFAP3 protein, human; D011990:Receptors, Transferrin