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Microtubules, Acetylation, and MEC-3 Regulated Genes in C. Elegans Mechanosensations

Charles Clifford Keller

Title:
Microtubules, Acetylation, and MEC-3 Regulated Genes in C. Elegans Mechanosensations
Author(s):
Keller, Charles Clifford
Thesis Advisor(s):
Chalfie, Martin
Date:
Type:
Dissertations
Department:
Biological Sciences
Permanent URL:
Notes:
Ph.D., Columbia University.
Abstract:
The ability to transform physical energies from internal and external environments into neuronal signals underlies the senses of hearing and touch as well as many aspects of body self-awareness. The small soil dwelling nematode Caenorhabditis elegans has proven to be a useful system in which to study neuronal mechanosensation and the development of specialized neuronal subtypes. Response to gentle body touch in C. elegans is mediated by the six Touch Receptor Neurons (TRNs). TRN cell fate is specified by the LIM-Homeodomain transcription factor MEC-3. Gene expression profiling has revealed a set of putatively MEC-3 dependant transcripts, which may represent the set of genes necessary to establish a TRN fate. I characterized this set of putatively MEC-3 regulated transcripts confirming the MEC-3 dependant expression of several previously unrecognized MEC-3 targets providing insight into TRN development and function and identifying the CCT chaperonin complex as being needed for TRN function. LIM-HD transcription factors play important developmental roles across phyla particularly in neurons. The data presented in this thesis provide insight into LIM-HD function in general and provide targets for further research in C. elegans TRNs as well as neurons from higher organisms. Microtubules (MTs) play crucial roles in the majority of eukaryotic cells where they are required for cell division, intracellular transport, morphological stability and a variety of other functions. The TRNs of C. elegans are characterized by unique large-diameter, heavily acetylated microtubules (MTs), which are required for mechanosensation. The TRNs thus present a valuable model for the study of neuronal MTs and MT acetylation, which is a poorly understood but widespread MT modification particularly in post-mitotic neurons. I employed TRN-specific RNAi to identify MT-associated proteins not previously known to be involved with mechanosensation including the CCPP-1 tubulin deglutamylase, the C. elegans homolog of the MT severing enzyme katanin, and several other proteins. I also shed light on the significance of á-tubulin acetylation by investigating the acetyltransferases responsible. MEC-17 and ATAT-2 are á-tubulin acetyltransferases found in the TRNs, which illustrate mechanosensory defects when mutated. I found that mec-17 mutants exhibit a drastic decrease in TRN MT number as well as an elimination of the unknown electron-dense material found in the lumen of TRN MTs and other MTs across phyla. I also found that eliminating MEC-17 activity changed TRN morphology, resulting in ectopic sprouting and process growth. These results suggest that acetyltransferase activity is required for TRN MT integrity, mechanosensory function, and the maintenance of TRN morphology.
Subject(s):
Biology
Neurosciences
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