Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton.
Myosin VI, an actin-based motor protein, and Disabled 2 (Dab2), a molecule involved in endocytosis and cell signalling, have been found to bind together using yeast and mammalian two-hybrid screens. In polarised epithelial cells, myosin VI is known to be associated with apical clathrin-coated vesicles and is believed to move them towards the minus end of actin filaments, away from the plasma membrane and into the cell. Dab2 belongs to a group of signal transduction proteins that bind in vitro to the FXNPXY sequence found in the cytosolic tails of members of the low-density lipoprotein receptor family. The central region of Dab2, containing two DPF motifs, binds to the clathrin adaptor protein AP-2, whereas a C-terminal region contains the binding site for myosin VI. This site is conserved in Dab1, the neuronal counterpart of Dab2. The interaction between Dab2 and myosin VI was confirmed by in vitro binding assays and coimmunoprecipitation and by their colocalisation in clathrin-coated pits/vesicles concentrated at the apical domain of polarised cells. These results suggest that the myosin VI-Dab2 interaction may be one link between the actin cytoskeleton and receptors undergoing endocytosis.
Morris
Shelli M
SM
Fred Hutchinson Cancer Research Center, Division of Basic Sciences, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA.
Arden
Susan D
SD
Roberts
Rhys C
RC
Kendrick-Jones
John
J
Cooper
Jonathan A
JA
Luzio
J Paul
JP
Buss
Folma
F
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003599:Cytoskeleton / Q000378:metabolism*; D004705:Endocytosis; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D011506:Proteins; D025521:Tumor Suppressor Proteins; C089785:myosin VI; D018995:Myosin Heavy Chains