Tctex-1, a novel interaction partner of Rab3D, is required for osteoclastic bone resorption.
Mol Cell Biol
; 31(7): 1551-64, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21262767
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.
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Banco de datos:
MEDLINE
Asunto principal:
Osteoclastos
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Resorción Ósea
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Dineínas
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Proteínas de Unión al GTP rab3
Límite:
Animals
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Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article