<i>Caenorhabditis elegans</i> touch receptor neuron development and function: The roles of microtubules, a MAP kinase pathway, and an F -box protein
The ability of animals to sense and respond to force requires the development of specialized mechanosensory neurons. In the nematode Caenorhabditis elegans, response to gentle body stimuli is mediated by six touch receptor neurons. These neurons are characterized by unique large-diameter microtubules that associate in bundles. This thesis continues the study of these neurons, concentrating on proteins needed for their development and function.
Previous work has shown requirements for the large-diameter microtubules in touch sensitivity and intracellular transport, but their functions in touch receptor neurons remain poorly understood. Using mutations in the mec-7 and mec-12 genes, which encode the tubulins that comprise these specialized microtubules, as well as drugs that selectively depolymerize microtubules in the touch receptor neurons, I further characterized their roles in transport and demonstrate a novel function for the microtubules in regulating gene expression through a p38 MAP kinase pathway. Furthermore, I provide evidence of a specific role for microtubules in mechanosensation that is separate from their developmental functions in transport and gene expression.
This thesis also describes the molecular cloning and characterization of MEC-15, an F-box protein needed for touch neuron sensitivity, synapse formation, and morphogenesis. Interestingly, mec-15 mutant defects are dependent on MEC-7 levels. I propose that MEC-15 functions to modulate mechanosensation, synaptogenesis, and cell shape by negatively regulating proteins that affect cytoskeletal organization. In addition, mutations in the same p38 MAP kinase pathway described above enhance all mec-15 phenotypes, indicating that MEC-15 works in parallel to this pathway to affect these processes.
In summary, I demonstrate roles for specialized microtubules, p38 MAP kinase signaling, and the MEC-15 F-box protein in both development and function of the touch neurons. Some processes appear to require collaboration between all three components. Taken together, these studies help characterize proteins needed for mechanosensation and shed light on the complex picture of touch receptor neuron differentiation.
0379: Cellular biology