First Author | Pavlos NJ | Year | 2011 |
Journal | Mol Cell Biol | Volume | 31 |
Issue | 7 | Pages | 1551-64 |
PubMed ID | 21262767 | Mgi Jnum | J:170764 |
Mgi Id | MGI:4947323 | Doi | 10.1128/MCB.00834-10 |
Citation | Pavlos NJ, et al. (2011) Tctex-1, a Novel Interaction Partner of Rab3D, Is Required for Osteoclastic Bone Resorption. Mol Cell Biol 31(7):1551-64 |
abstractText | 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. |