Abstract
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.
Highlights
Dendrites and axons are two distinct functional and morphological domains of neurons
We have examined membrane trafficking in the PVD neuron in the nematode worm C. elegans to investigate how new membrane and dendrite proteins are trafficked
We have discovered that a key organizer of vesicle trafficking, the RAB-10 protein, localizes to membrane vesicles and is required to traffic these vesicles that contain plasma membrane and dendrite proteins to the growing PVD dendrite
Summary
Dendrites and axons are two distinct functional and morphological domains of neurons. In Drosophila, loss-of-function mutations in genes encoding the small GTPases Rab and Sar, which are key regulators of ER-to-Golgi vesicular transport [3], severely reduce the growth of dendrites. Loss of Rab and Sar do not diminish axon outgrowth, suggesting that the mechanisms underlying the extension of dendrites and axon are distinct [1]. Golgi outposts, which are primarily found in dendrites but not axons, play an important role in supplying membranes for dendritic branching and growth [1]. These experiments suggest that membrane components generated in the ER and trafficked to the Golgi are essential for dendritic growth. The molecular mechanisms that deliver membranes from the Golgi, Golgi-outposts and endosomes to the dendritic plasma membrane, are unclear
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