MSC Graduate Seminar-Yael Iosilevskii
02/09/2019 13:00

Research Topic:

Functions for git-1in dendritic maintenance and behavior in Caenorhabditis elegans

The protein GIT1 (G-protein-coupled receptorkinase interacting ArfGAP 1) is a GTPase activating protein (GAP) for the Arfsmall GTP-binding proteins, and a focal-adhesion-based scaffold, with over 100associated proteins. GIT1 has been linked to dendritic spine formation andsynaptic changes in rodent hippocampus, as well as impairment in fear responseand learning. It has also been implicated in Huntington’s disease,Schizophrenia, and ADHD (reviewed in 1). Inorder to study the effects of GIT1 on dendritic morphology, we use C.elegansand its stereotypically-arborized polymodal neuron PVD (2) and follow its dendritic arborizationpattern and associated behavioral outputs. We found that while git-1mutantsdisplay relatively normal PVD neuron morphology in L4 stage, this is followedby a significant and asymmetric increase in tertiary and quaternary ectopicbranches during early adulthood. Thus, git-1 isnecessary for dendritic maintenance, but not morphogenesis. To reveal thesignaling pathway mediating this effect, we tested mutants of the GIT-1 primarybinding partner PIX (p21-activated kinase [PAK]-interacting exchange factor)and its downstream kinase PAK. We found that pix-1mutants have a similar, yet milder, phenotype in adult PVD morphology, but pak-1 andhomologue max-2 mutants are wild-type-like, suggestingthat git-1 acts partly through its binding partner pix-1 as anegative regulator of branch arborization in adulthood. The behavioralphenotypes associated with git-1 weretested by movement analysis and a harsh touch response assay, where we showthat two git-1 mutant alleles have no apparentmechanosensory defects but display increased speed and body wavelength. Theseresults open a possibility for a novel dendritic maintenance pathway, which mayinfluence proprioceptive faculties in the worm.