Multiple roles for UNC-53/NAV2 in cell migration, trafficking and innate immunity in Caenorhabditis elegans

unc-53 is the Caenorhabditis elegans homolog of Nav2, and a member of the Neuron Navigator protein family, a group of cytoskeletal binding proteins with conserved roles in the guidance and outgrowth of cells and cellular processes. The signalling pathways that employ UNC-53 during development, and the role of UNC-53 after development is complete, are largely unknown. A proteomics screen for interactors of UNC-53 identified that UNC-53 interacts with ABI-1. The Calponin Homology domain unique to the long-isoform of UNC-53 is sufficient to bind ABI-1 in vitro and is required in vivo for longitudinal migration. ABI-1 and UNC-53 are co-expressed, and abi-1 genetic loss causes many of the same migration defects as unc-53 mutants. abi-1 and unc-53 function cell-autonomously and in a common genetic pathway in the posterior migration of the excretory canals, and genetically inactivating abi-1 interactors (nck-1, wve-1, arx-2) resulted in phenotypes similar to unc-53 and abi-1. abi-1 and unc-53 are also required for endocytosis as measured by assaying the in vivo uptake of GFP into coelomocytes and primary oocytes. Lastly, abi-1 mutants have unc-53 independent migration defects, and ABI-1 binds to MIG-10A through its SH3 domain, thereby demonstrating that ABI-1 interacts with two proteins that function cell-autonomously in the longitudinal migration of the excretory canals. To identify a post-developmental role for unc-53, a potential role for unc-53 in innate immunity was assessed. unc-53 mutants are susceptible to the human and nematode pathogen Pseudomonas aeruginosa PA14. unc-53 mutants are hypersensitive to Aldicarb and have increased RNA levels of the daf-16 antagonist ins-7 as well as decreased nuclear DAF-16 localization following recovery from cellular stress, suggesting that unc-53 functions in the daf-16 pathway. Loss of function and null alleles of daf-2 and ins-7 only partially suppress unc-53 in immunity, and a null pmk-1 mutant does not enhance unc-53. Together, this data suggests that unc-53 participates in innate immunity through multiple tissues, isoforms and genetic pathways. These findings expand on the varied functions of unc-53 and the signal transduction pathways that it controls, opening up new prospects for future areas of research.