The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1

Abstract

The shape changes that are required to position a cell to migrate or grow out in a particular direction involve a coordinated reorganization of the actin cytoskeleton. Although it is known that the ARP2/3 complex nucleates actin filament assembly, exactly how the information from guidance cues is integrated to elicit ARP2/3-mediated remodeling during outgrowth remains vague. Previous studies have shown that C. elegans UNC-53 and its vertebrate homolog NAV (Neuronal Navigators) are required for the migration of cells and neuronal processes. We have identified ABI-1 as a novel molecular partner of UNC-53/NAV2 and have found that a restricted calponin homology (CH) domain of UNC-53 is sufficient to bind ABI-1. ABI-1 and UNC-53 have an overlapping expression pattern, and display similar cell migration phenotypes in the excretory cell, and in mechanosensory and motoneurons. Migration defects were also observed after RNAi of proteins known to function with abi-1 in actin dynamics, including nck-1, wve-1 and arx-2. We propose that UNC-53/NAV2, through its CH domain, acts as a scaffold that links ABI-1 to the ARP2/3 complex to regulate actin cytoskeleton remodeling.

Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

“…UNC-53 is required cell autonomously to control the outgrowth of the excretory canals as full-length unc-53 cDNA driven by the ppgp-12 excretory cell-specific promoter is sufficient to rescue the canal outgrowth defects of unc-53 (n166) mutants ( Figure 1G; Stringham et al 2002;Schmidt et al 2009). To determine whether vab-8 also functions cell autonomously we expressed the long isoform of VAB-8 (VAB-8L) specifically in the excretory cell under the control of the ppgp-12 EC-specific promoter.…”

“…In unc-53 (n166) mutants, a null allele, the EC body is positioned normally with respect to the posterior pharyngeal bulb, but both the anterior and posterior canals are severely truncated (Figure 1B; Schmidt et al 2009). The anterior processes terminate close to the EC body and do not extend further than the anterior pharyngeal bulb, while the posterior canals grow out to the midbody, terminating at the level of the vulva ( Figure 1B; Schmidt et al 2009). Examination of the null mutant vab-8(e1017) revealed a failure of the majority of the posterior canals to exit the gonad region ( Figure 1C).…”

“…UNC-53 and the NAVs contain several cytoskeletal binding domains including an actinbinding calponin-homology domain, and putative microtubule binding domains (Stringham et al 2002). UNC-53 localizes to the cytoskeleton, binds F-actin in vitro, and binds ABI-1(Abelson kinase interactor 1), a regulator of ARP2/3-mediated actin filament assembly (Stringham et al 2002;Schmidt et al 2009). UNC-53 may also function in signal transduction as it is known to genetically and physically interact with the SH2-SH3 adapter protein SEM-5/GRB-2, a mediator of EGL-15/FGFR signaling in sex myoblast migration in C. elegans Stringham et al 2002).…”

Neuron navigator 3a regulates liver organogenesis during zebrafish embryogenesis

“…Unc-53 in C. elegans encodes a neural guidance factor required for axon elongation and cell migration (Maes et al, 2002;Schmidt et al, 2009;Stringham et al, 2002). In mammals, three unc-53 homolog genes exist: neuron navigator 1, 2 and 3 (Nav1, Nav2 and Nav3) (Maes et al, 2002).…”

“…In mammals, three unc-53 homolog genes exist: neuron navigator 1, 2 and 3 (Nav1, Nav2 and Nav3) (Maes et al, 2002). Both the unc-53 gene in C. elegans and Nav3 in rat and human have different isoforms (Maes et al, 2002;Peeters et al, 2004;Schmidt et al, 2009). Intracellular protein localization, tissue specific expression and differential relevance of UNC-53 or Nav3 protein isoforms have not been clarified so far.…”