|M.Sc Student||Iosilevskii Yael|
|Subject||Functions for git-1 in Dendritic Maintenance and Behavior in|
|Department||Department of Biology||Supervisor||Professor Benjamin Podbilewicz|
|Full Thesis text|
The protein GIT1 (G-protein-coupled receptor kinase interacting ArfGAP 1) is a GTPase activating protein (GAP) for the Arf (ADP ribosylation factor) small GTP-binding proteins, and a focal-adhesion-based scaffold, with over 100 associated proteins. Mutations in GIT1 have been linked to reduced dendritic spine formation and synaptic changes in rodent hippocampus, as well as impairment in fear response and learning. It has also been implicated in Huntington’s disease, Schizophrenia, and ADHD. In order to study the effects of GIT1 on dendritic morphology, we use C. elegans and its stereotypically-arborized polymodal neuron PVD and follow its dendritic arborization pattern and associated behavioral outputs. We found that while git-1 mutants display some ectopic branching of the PVD neuron in L4 stage, this is followed by a significant and dorsoventral asymmetric increase in ectopic branches during early adulthood. Thus, git-1 is necessary primarily for dendritic maintenance, with milder effects on morphogenesis. To reveal the signaling pathway mediating this effect, we tested mutants of the GIT1 primary binding partner PIX (p21-activated kinase [PAK]-interacting exchange factor) and its downstream kinase PAK. We found that pix-1 mutants have a similar, yet milder, phenotype in adult PVD morphology, but pak-1 and homologue max-2 mutants are wild-type-like, suggesting that git-1 acts partly through its binding partner pix-1 as a negative regulator of branch arborization in adulthood. The behavioral phenotypes associated with git-1 were tested by movement analysis and a harsh touch response assay, where we show that two git-1 mutant alleles have no apparent mechanosensory defects but display increased speed and movement wavelength. These results open a possibility for a novel dendritic maintenance pathway, which may influence proprioceptive faculties in the worm.