Title | Tctex-1, a novel interaction partner of Rab3D, is required for osteoclastic bone resorption. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Pavlos NJ, Cheng TSum, Qin A, Ng PYing, Feng H-T, Ang ESM, Carrello A, Sung C-H, Jahn R, Zheng M-H, Xu J |
Journal | Mol Cell Biol |
Volume | 31 |
Issue | 7 |
Pagination | 1551-64 |
Date Published | 2011 Apr |
ISSN | 1098-5549 |
Keywords | Amino Acid Sequence, Animals, Biological Transport, Bone Resorption, Cell Line, Dyneins, Gene Expression Regulation, Gene Knockdown Techniques, Guanosine Triphosphate, Humans, Mice, Microtubules, Molecular Sequence Data, Osteoclasts, Osteogenesis, Protein Binding, rab3 GTP-Binding Proteins, RNA Interference, RNA, Small Interfering, Secretory Vesicles |
Abstract | Vesicular transport along microtubules must be strictly regulated to sustain the unique structural and functional polarization of bone-resorbing osteoclasts. However, the molecular mechanisms bridging these vesicle-microtubule interactions remain largely obscure. Rab3D, a member of the Rab3 subfamily (Rab3A/B/C/D) of small exocytotic GTPases, represents a core component of the osteoclastic vesicle transport machinery. Here, we identify a new Rab3D-interacting partner, Tctex-1, a light chain of the cytoplasmic dynein microtubule motor complex, by a yeast two-hybrid screen. We demonstrate that Tctex-1 binds specifically to Rab3D in a GTP-dependent manner and co-occupies Rab3D-bearing vesicles in bone-resorbing osteoclasts. Furthermore, we provide evidence that Tctex-1 and Rab3D intimately associate with the dynein motor complex and microtubules in osteoclasts. Finally, targeted disruption of Tctex-1 by RNA interference significantly impairs bone resorption capacity and mislocalizes Rab3D vesicles in osteoclasts, attesting to the notion that components of the Rab3D-trafficking pathway contribute to the maintenance of osteoclastic resorptive function. |
DOI | 10.1128/MCB.00834-10 |
Alternate Journal | Mol. Cell. Biol. |
PubMed ID | 21262767 |
PubMed Central ID | PMC3135285 |
Grant List | R01 EY011307 / EY / NEI NIH HHS / United States EY11307 / EY / NEI NIH HHS / United States |