"Cell and process migration are critical to the establishment of neural circuitry. The study of these processes is facilitated through use of model organisms with simple nervous systems, such as C. elegans. Research in this nematode has defined the cytoplasmic adaptor MIG-10 as a key regulator of these processes. Mutation of mig-10 disrupts neuronal and axonal migration and outgrowth of the ‘canals’, or processes, of the excretory cell. MIG-10 directs the localization of UNC-34, which remodels actin filaments at the leading edge of a migrating cell or process to modify the direction or rate of its protrusion. An interactor of MIG-10 identified in a yeast two- hybrid analysis, ABI-1, has several roles in actin remodeling, such as targeting Ena/VASP members for phosphorylation by Abl kinase. Mutation of abi-1 in the nematode produces phenotypes that resemble those of mig-10 mutants, including disrupted outgrowth of the excretory canals, a developmental process in which ABI-1 is known to function cell autonomously. To test the hypothesis that the ABI-1/MIG-10 interaction contributes to cell migration and outgrowth, both in vivo and in vitro analyses were performed. Expression of either MIG-10A or MIG-10B exclusively in the excretory cell partially rescued the canal truncation characteristic of mig-10 mutants, suggesting MIG-10 functions autonomously in this cell during canal outgrowth. Physical interaction between MIG-10 and ABI-1 was confirmed using a co-immunoprecipitation system. Both MIG-10A and MIG-10B interact with ABI-1 through a mechanism that likely involves the SH3 domain of ABI-1 and sites in either the central region or C-terminus of MIG-10. These results suggest that MIG-10 and ABI-1 function together in a cell autonomous manner to promote cell or process migration. A possible consequence of this interaction is modulation of the MIG-10 binding to UNC-34 through Abl-mediated phosphorylation of MIG-10."
| Identifer | oai:union.ndltd.org:wpi.edu/oai:digitalcommons.wpi.edu:etd-theses-1982 |
| Date | 26 August 2011 |
| Creators | McShea, Molly A |
| Contributors | Elizabeth F. Ryder, Advisor, Luis Vidali, Committee Member, Joseph B. Duffy, Committee Member |
| Publisher | Digital WPI |
| Source Sets | Worcester Polytechnic Institute |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Masters Theses (All Theses, All Years) |
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