The ubiquitin-proteasome system mediates selective degradation of intracellular proteins. In this system, a cascade of enzymatic reactions by the ubiquitin-activating enzyme (E1), the ubiquitin-conjugating enzyme (E2), and the ubiquitin ligase (E3) leads to the covalent attachment of a single, or a chain of ubiquitin(s) to a lysine residue of a substrate, thus targeting the substrate for proteasomal degradation. The C. elegans genome encodes for one E1, roughly twenty E2s, and hundreds of E3s. Among the E2 ubiquitin-conjugating enzymes is UBC-1; however, its function in C. elegans remains elusive. Studies of UBC-1 orthologs in human, fruit fly, and yeast suggest it may have significant function in the nervous system. UBC-1 orthologs (RAD6a/Ube2a) have been shown to be necessary for mitochondrial function in neurons (Haddad et al., 2013). Moreover, mutations in human RAD6a/Ube2a have been associated with X-linked intellectual disability (XLID) (Budny et al., 2010; Honda et al., 2010).Here we elucidate the role of UBC-1 in nervous system development in a C. elegans
ubc-1 mutant isolated in the laboratory.
ubc-1 mutants possess poor general health, decreased brood size, and synaptic defects. These defects can be rescued significantly, but not completely by expressing UBC-1 either in all neurons or in intestinal cells. These results suggest that UBC-1 has an important role in the nervous system, but also hints at possible cross-talk between the nervous system and intestine. This study sets the foundation for future studies to investigate the mechanisms by which mutations in UBC-1 may lead to disease.Budny, B., Badura-Stronka, M., Materna-Kiryluk, A., Tzschach, A., Raynaud, M., Latos-Bielenska, A., and Ropers, H.H. (2010). Novel missense mutations in the ubiquitination-related gene UBE2A cause a recognizable X-linked mental retardation syndrome. Clin. Genet. 77, 541-551.Honda, S., Orii, K.O., Kobayashi, J., Hayashi, S., Imamura, A., Imoto, I., Nakagawa, E., Goto, Y., and Inazawa, J. (2010). Novel deletion at Xq24 including the UBE2A gene in a patient with X-linked mental retardation. J. Hum. Genet. 55, 244-247.Haddad D.M., Vilain,S., Vos, M., Esposito, G., Matta, S., Kalscheuer, V.M., Craessaerts, K., Leyssen, M., Nascimento, R.M.P., Vianna-Morgante, A.M. De Strooper, B., Van Esch, H., Morais, V.A. and Verstreken, P. (2013). Mutations in the intellectual disability gene Ube2a cause neuronal dysfunction and impair Parkin-dependent mitophagy. Mol. Cell 50(6), 831-843.