Rhodopsin's carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1.
The interaction of cytoplasmic dynein with its cargoes is thought to be indirectly mediated by dynactin, a complex that binds to the dynein intermediate chain. However, the roles of other dynein subunits in cargo binding have been unknown. Here we demonstrate that dynein translocates rhodopsin-bearing vesicles along microtubules. This interaction occurs directly between the C-terminal cytoplasmic tail of rhodopsin and Tctex-1, a dynein light chain. C-terminal rhodopsin mutations responsible for retinitis pigmentosa inhibit this interaction. Our results point to an alternative docking mechanism for cytoplasmic dynein, provide novel insights into the role of motor proteins in the polarized transport of post-Golgi vesicles, and shed light on the molecular basis of retinitis pigmentosa.
Tai
A W
AW
Department of Cell Biology and Anatomy, Margaret M. Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, New York 10021, USA.
Chuang
J Z
JZ
Bode
C
C
Wolfrum
U
U
Sung
C H
CH
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002417:Cattle; D003593:Cytoplasm / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D051379:Mice; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism*; D056427:t-Complex Genome Region
C533386:Dynlt1b protein, mouse; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D012243:Rhodopsin; D004398:Dyneins