Transcription regulatory networks in Caenorhabditis elegans

unc-50 encodes an integral membrane protein orthologous to the Saccharomyces cerevisiae Golgi component Gmh1p; UNC-50 is required for regulating subtype-specific nicotinic receptor trafficking to the cell surface and thus, for normal synaptic transmission at the neuromuscular junction; UNC-50 is ubiquitously expressed from early embryogenesis to adulthood and localizes to the Golgi.

unc-42 encodes a paired-like homeodomain protein of the Q50 class; UNC-42 is required to specify the fate of ASH sensory neurons, AVA, AVD, and AVE interneurons, and a subset of motor neurons; unc-42 mutants fail to express cell-surface receptors required for differentiated neuronal function (sra-6, srb-6, glr-1, glr-5, and glr-6); UNC-42 is also required for AVKR and HSNL growth cones to follow the PVPR and PVQL pioneer axons, for axonal outgrowth in the backward command interneurons AVA, AVD, and AVE, and for inhibition of ectopic FMRFamide-positive and GABAergic axons; unc-42 mutants are defective in mechanosensation, backward motion, and regulation of egg-laying.

unc-38 encodes a nicotinic acetylcholine receptor (nAChR) alpha subunit; UNC-38 is required for normal locomotion and egg-laying, and functions as a subunit of a ligand-gated ion channel that likely mediates fast actions of acetylcholine at neuromuscular junctions and in the nervous system; when coexpressed with ACR-2, ACR-3, UNC-29, and LEV-1, non-alpha nAChR subunits, the resulting multimer can form levamisole-gated channels; UNC-38 is expressed postsynaptically in muscles and neurons where it colocalizes with TAX-6, and with ACR-8, ACR-12, and UNC-29, respectively.

unc-32 encodes, by alternative splicing, six isoforms of an ortholog of subunit a of the membrane-bound (V0) domain of vacuolar proton-translocating ATPase (V-ATPase); UNC-32 is orthologous to human ATP6N1A (OMIM:192130), ATP6V0A2, ATP6V0A4 (OMIM:605239, mutated in distal renal tubular acidosis), and TCIRG1 (OMIM:604592, mutated in osteopetrosis); one UNC-32 isoform is essential for locomotion and normal synaptic vesicle morphology in motoneurons, is expressed solely in the nervous system, and is specifically mutated by unc-32(e189) or unc-32(f120); other UNC-32 isoforms are essential for embryonic and larval development; UNC-32 is expressed throughout the life cycle, strongly in the nervous system, but also in vulvae, spermathecal-uterine valves, and pharynx; UNC-32 is required for necrosis, since mutations of unc-32 suppress necrotic neurodegeneration and thapsigargin-induced cell death; in S. cerevisiae, different V0 a-subunits (Stv1p and Vph1p) direct the assembly of V-ATPases to different membranes and organelles, suggesting that the profusion of such subunits in C. elegans (co-orthologous VHA-5, VHA-6, VHA-7, and six UNC-32 isoforms) may have a similar function; UNC-32 is predicted to capture protons from V-ATPase transmembrane rotor components and export the protons across the membrane.

unc-27 encodes a troponin I isoform; unc-27 is required for coordinated motility and normal muscle morphology; structural analyses indicate that unc-27 is required for proper sarcomeric organization; unc-27/troponin I interacts with the body wall and pharynx types of troponin C; expression studies show that unc-27 is expressed in body wall, vulval and anal muscles.

unc-18 encodes an ortholog of Saccharomyces cervisiae SEC1 that enables the docking of vesicles to synaptic regions before vesicle priming and fusion, and thus promotes synaptic vesicle exocytosis; UNC-18 may also inhibit excessive exocytosis.

unc-108 encodes a small GTPase homologous to the Rab GTPases that function in endocytosis, membrane fusion, and vesicular trafficking events; unc-108 function is required in neurons for normal locomotion; unc-108 also functions in the removal of apoptotic cells, specifically it functions in engulfing cells for the recruitment and fusion of the lysosome to the phagosome; unc-108 is expressed in neurons and in engulfing cells.

ubq-2 encodes a bifunctional protein that contains two domains; an N-terminal ubiquitin peptide, and a C-terminal large ribosomal subunit protein L40 peptide.

ubc-7 encodes an E2 ubiquitin-conjugating enzyme; by homology, UBC-7 is predicted to function in the covalent attachment of ubiquitin molecules to protein substrates via its association with an E3 ubiquitin-protein ligase; loss of ubc-7 activity via large-scale RNAi screens results in no obvious abnormalities.

ubc-18 encodes an E2 ubiquitin-conjugating enzyme related to human UBCH7 (OMIM:603731); UBC-18 activity is required for normal growth and reproduction, and UBC-18 functions redundantly with LIN-35/Rb and other class B synthetic multivulval (SynMuv) gene products to regulate pharyngeal morphogenesis during embryonic development; ubc-18 transcripts are detected in the germline, embryos, late larval stages, and adults, suggesting that UBC-18 may function maternally to regulate several aspects of C. elegans development; the substrates of UBC-18 are not yet known.