Interaction of Doc2 with tctex-1, a light chain of cytoplasmic dynein. Implication in dynein-dependent vesicle transport.
Doc2 has one Munc13-interacting domain at the N-terminal region and two C2-like domains interacting with Ca2+ and phospholipid at the C-terminal region. Doc2 consists of two isoforms, Doc2alpha and -beta. Doc2alpha is specifically expressed in neuronal cells and implicated in Ca2+-dependent neurotransmitter release, whereas Doc2beta is ubiquitously expressed and its function is unknown. We show here that both Doc2alpha and -beta interact with rat tctex-1, a light chain of cytoplasmic dynein, in both cell-free and intact cell systems. Overexpression of the N-terminal fragment of Doc2 containing the tctex-1-interacting domain induces changes in the intracellular localization of cation-independent mannose 6-phosphate receptor and its ligand, cathepsin D, which are transported from trans-Golgi network to late endosomes. Overexpression of the C-terminal fragment containing two C2-like domains shows the similar effect, but to a lesser extent, whereas overexpression of full-length Doc2 or the C-terminal fragment of rabphilin3 containing two C2-like domains does not show this effect. Because dynein is a minus-end-directed microtubule-based motor protein, these results suggest that Doc2, especially Doc2beta, plays a role in dynein-dependent intracellular vesicle transport.
Nagano
F
F
Department of Molecular Biology and Biochemistry, University Medical School, Suita, Japan.
Orita
S
S
Sasaki
T
T
Naito
A
A
Sakaguchi
G
G
Maeda
M
M
Watanabe
T
T
Kominami
E
E
Uchiyama
Y
Y
Takai
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism; D006224:Cricetinae; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D008868:Microtubule Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D011485:Protein Binding; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D056427:t-Complex Genome Region
D002135:Calcium-Binding Proteins; C091524:DOC2A protein, human; C490420:DOC2B protein, human; C490419:Doc2a protein, rat; C533388:Dynlt1 protein, rat; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D017527:Receptor, IGF Type 2; D002402:Cathepsin D; D004398:Dyneins