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PLoS Genet ; 11(9): e1005484, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26394140

RESUMO

Formation of elaborately branched dendrites is necessary for the proper input and connectivity of many sensory neurons. Previous studies have revealed that dendritic growth relies heavily on ER-to-Golgi transport, Golgi outposts and endocytic recycling. How new membrane and associated cargo is delivered from the secretory and endosomal compartments to sites of active dendritic growth, however, remains unknown. Using a candidate-based genetic screen in C. elegans, we have identified the small GTPase RAB-10 as a key regulator of membrane trafficking during dendrite morphogenesis. Loss of rab-10 severely reduced proximal dendritic arborization in the multi-dendritic PVD neuron. RAB-10 acts cell-autonomously in the PVD neuron and localizes to the Golgi and early endosomes. Loss of function mutations of the exocyst complex components exoc-8 and sec-8, which regulate tethering, docking and fusion of transport vesicles at the plasma membrane, also caused proximal dendritic arborization defects and led to the accumulation of intracellular RAB-10 vesicles. In rab-10 and exoc-8 mutants, the trans-membrane proteins DMA-1 and HPO-30, which promote PVD dendrite stabilization and branching, no longer localized strongly to the proximal dendritic membranes and instead were sequestered within intracellular vesicles. Together these results suggest a crucial role for the Rab10 GTPase and the exocyst complex in controlling membrane transport from the secretory and/or endosomal compartments that is required for dendritic growth.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Dendritos/genética , Plasticidade Neuronal/genética , Células Receptoras Sensoriais/metabolismo , Proteínas rab de Ligação ao GTP/genética , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/metabolismo , Dendritos/fisiologia , Endocitose/genética , Retículo Endoplasmático/genética , Endossomos/genética , Complexo de Golgi/genética , Proteínas de Membrana/genética , Moduladores de Transporte de Membrana/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
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