The EGL-21 carboxypeptidase E facilitates acetylcholine release at Caenorhabditis elegans neuromuscular junctions.
Proneuropeptides are packaged into dense-core vesicles in which they are processed into active peptides by copackaged enzymes. Proprotein convertases (PCs) cleave precursors after dibasic residues, and carboxypeptidases remove basic residues from the C terminals. We show here that the Caenorhabditis elegans egl-21 gene encodes a protein that is very similar to carboxypeptidase E (CPE) and is broadly expressed in the nervous system. Mutants lacking either egl-21 CPE or egl-3, which encodes the C. elegans ortholog of PC type 2 (PC2), were defective for processing endogenously expressed FMRFamide (Phe-Met-Arg-Phe-NH2)-related peptides (FaRPs). Mutants lacking the unc-104 kinesin motor protein were defective for anterograde movement of dense-core vesicle components, including egl-3 PC2, egl-21 CPE, and FaRPs. We provide evidence that egl-3 PC2 and egl-21 CPE mutants have diminished acetylcholine release at neuromuscular junctions (NMJs). Taken together, these results suggest that egl-21 CPE and egl-3 PC2 process endogenous neuropeptides that facilitate acetylcholine release at C. elegans NMJs.
Jacob
Tija C
TC
Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California 94720, USA.
Kaplan
Joshua M
JM
D000109:Acetylcholine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D019835:FMRFamide / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D009928:Organ Specificity; D045706:Proprotein Convertase 2; D011499:Protein Processing, Post-Translational; D022142:Secretory Vesicles / Q000378:metabolism; D016415:Sequence Alignment; D013381:Subtilisins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C423186:UNC-104 protein, C elegans; D019835:FMRFamide; D002268:Carboxypeptidases; D043423:Carboxypeptidase H; D013381:Subtilisins; C473666:EGL-3 proprotein convertase, C elegans; D045706:Proprotein Convertase 2; D000109:Acetylcholine