Transcription regulatory networks in Caenorhabditis elegans

aman-3 encodes a Co(II)-activated alpha-mannosidase II, orthologous to human MAN2C1; AMAN-3 is predicted to remove mannose residues from the N-linked oligosaccharides of glycoproteins; AMAN-3 contains three predicted N-glycosylation sites; AMAN-3 is biochemically active in vitro, with a pH optimum of 6.5; AMAN-3 requires either Co(II) or Mn(II) for activity, preferring the former ion; since aman-2(tm1078) mutants almost completely lack paucimannosidic glycans, the function of AMAN-3 in vivo is unclear.

amt-3 encodes one of four C. elegans homologs of AMT1 (AT11_ARATH), a high-affinity ammonium transporter from Arabidopsis thaliana; AMT-3 is closely similar to its paralog AMT-2, with somewhat more distant paralogy to AMT-1 and AMT-4.

apa-2 encodes an adaptin: specifically, it encodes an ortholog of the alpha subunit of adaptor protein complex 2 (AP2); loss of apa-2 activity via RNAi results in defects in receptor-mediated yolk endocytosis and thus, embryonic lethality.

apc-2 encodes an ortholog of subunit 2 of anaphase-promoting complex (APC, a cyclin-specific E3 RING ubiquitin ligase); APC-2 and S. cerevisiae's Apc2p have 32% identity in their cullin domains (considered crucial for function), but otherwise share no obvious similarity; inactivating apc-2 with RNAi causes embryos to arrest at the meiotic one-cell stage, implying that APC-2 is required for the metaphase-to-anaphase transition of meiosis I; this RNAi phenotype of apc-2 is shared by apc-1, apc-4, apc-11, cdc-16, cdc-23, and cdc-27; by analogy with other APC subunits with hypomorphic alleles, APC-2 is likely to be required for asymmetrical segregation of cell fate determinants in two-cell embryos.

apl-1 encodes two almost identical isoforms orthologous to human APP (OMIM:104760, mutated in familial Alzheimer disease or cerebroarterial amyloidosis), APLP1 (OMIM:104775), and APLP2 (OMIM:104776); although native APL-1 is predicted to be membrane-bound until proteolytically cleaved, neuronal expression of a partial N-terminal extracellular region of APL-1 alone, containing either the E1 or the E2 domain, is sufficient for APL-1's normal functions in vivo (molting and morphogenesis, pharyngeal pumping, and progession past the L1 larval stage), indicating that APL-1 functions non-cell-autonomously; apl-1 is widely expressed in neurons, muscle, hypodermis, and supporting cells of larvae and adults; APL-1 contains a Cu(II)-binding domain; overexpressed APL-1 causes abnormal locomotion, infertility, and partial lethality, but the lethality of excess APL-1 can be partially suppressed by hypomorphic sel-12 mutations; apl-1 mutants show vacuoles in hypodermal cells, while having superfically normal neurons; apl-1 genetically interacts with feh-1 to affect pharyngeal pumping, and APL-1 binds the PTB2 domain of FEH-1 in vitro; apl-1 mutations are not suppressed by ced-3 or crt-1 mutations, and thus are unlikely to activate apoptosis or necrosis.

aps-2 encodes an adaptin: specifically, it encodes an ortholog of the sigma2 subunit of adaptor protein complex 2 (AP2), which mediates endocytosis from the plasma membrane; APS-2 is required for embryonic and larval development and for normal body morphogenesis, but is not required for endocytosis of yolk protein in developing oocytes; APS-2 is expressed in nearly all cells during embryogenesis, but during larval and adult stages, expression is confined to neurons and some hypodermal cells, including vulval hypodermal cells during the fourth larval stage.

aqp-1 encodes, by alternative splicing, two isoforms of an aquaglyceroporin required for normally short lifespan; AQP-1 expression is upregulated under daf-2(-) conditions, and loss of AQP-1 function in daf-2 mutant animals results in reduced lifespan; AQP-1 increases glycerol permeability five- to seven-fold when expressed in Xenopus oocytes; AQP-1::GFP fusion proteins are expressed predominantly in the intestine, where they localize to the basolateral plasma membrane, but are also expressed in the pharynx; intestinal expression of AQP-1 is repressed by infection with Pseudomonas aeruginosa.

aqp-2 encodes, by alternative splicing, two isoforms of an biochemically atypical aquaglyceroporin; when expressed in Xenopus oocytes, AQP-2 increases water permeability 5- to 11-fold, and urea permeability 4.5-fold, but has no effect on glycerol permeability; AQP-2::GFP fusion proteins are expressed predominantly in the excretory cell and more weakly in muscle, motor neurons, and hypodermis; AQP-2 expression is also enriched in dauer larvae; loss of AQP-2 activity via mutation or RNAi results in no obvious defects; however, AQP-2, in conjunction with AQP-3, AQP-4, and AQP-8, is weakly required for recovery from hypotonic stress.