TY - JOUR TI - Identification and characterization of components of rab-6-mediated trafficking in caenorhabditus elegans DO - https://doi.org/doi:10.7282/T3CF9RRC PY - 2014 AB - Membrane trafficking in neurons is an important mechanism used to regulate signaling. Controlling the abundance of AMPA-type receptors at the synapse is important for synaptic plasticity and influences processes involved in learning, memory formation, and motor control (Greger and Esteban, 2007; Shepherd and Huganir, 2007). In Caenorhabditis elegans, recycling of the AMPA receptor subunit GLR-1 has been demonstrated to be one method by which synaptic signaling mechanisms can be controlled. Rab GTPases 6.1 and 6.2 have been profiled for their role in trafficking of GLR-1 in neurons. RAB-6.2 plays a role in the retrograde trafficking of the AMPA-type glutamate receptor GLR-1 (Zhang et al., 2012). Activated Rab GTPases regulate membrane trafficking by recruiting multiple effectors, including proteins that modify phospholipid membrane composition, motor proteins that tether membranes to the cytoskeleton, and scaffolding proteins that bind to specific proteins within membranes (Stenmark, 2009). In order to understand RAB-6.2 function, we used a yeast two-hybrid approach to screen for candidate effector molecules. Herein, we discuss the screen performed and detail candidates of interest. We identified one particularly compelling candidate, a phosphoinositol-5-phosphatase named SAC-2, which we hypothesize to be involved in vesicle uncoating and/or in modifying membrane phospholipids. SAC-2::GFP is localized to punctate structures along the ventral nerve cord and in the neuron soma. SAC-2::GFP localization to puncta in the soma is enhanced in rab-6.2(ok2254) null mutant animals, which is opposite to our expectation for RAB-6.2 retrograde cargo or effector molecules. Additionally, we assessed the overlap in functions between RAB-6.1 and RAB-6.2, and delineating their pathways. In agreement with previous data from our lab, our findings suggest that the two RAB-6 isoforms perform similar trafficking functions, but do so independently of each other. KW - Microbiology and Molecular Genetics KW - Glutamic acid--Receptors LA - eng ER -