Intracellular transport and localization mechanisms of synaptic components in the nematode C. elegans.

摘要

Neurons, like all polarized cells, must regulate the transport and localization of many molecules to establish and maintain proper cellular function. Since one essential function of neurons is to communicate with other cells across specialized synaptic junctions, the localization of the molecular components that compose the synapse must be highly regulated. Within an individual neuron, the postsynaptic regions that receive information remain spatially separated from the presynaptic regions that send information. Mechanisms used to regulate the localization of synaptic components remain largely unknown, but are thought to involve regulated microtubule-dependent transport of vesicles containing the synaptic components from sites of synthesis via motor protein complexes. Although many synaptic components and motor proteins have been identified, how and which motors and cargoes interact remain questions of great interest. The simple nervous system of the nematode C. elegans provides a tractable genetic model for examining the regulated transport and localization mechanisms of synaptic components in vivo. Genetic screens utilizing a synaptic vesicle marker expressed in a subset of motor neurons have identified genes required for several different steps in neural development and synapse formation. The characterization of several genes required for proper transport and localization of synaptic vesicle markers and other synaptic components are described here, including genes encoding the UNC-16/JIP3/JSAP/dSYD JNK-signaling scaffold protein, JNK-signaling molecules (JKK-1 and JNK-1), the Kinesin-1 anterograde motor complex (UNC-116 and KLC-2), the KIF1A synaptic vesicle kinesin (UNC-104), and axon outgrowth signaling and cytoskeletal components (UNC-14, UNC-51, UNC-33, and UNC-44). Understanding their role in the simple nervous system of C. elegans will hopefully provide a basis for discerning their function in more complex mammalian nervous systems.