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PMID: 11717360 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The EGL-3 proprotein convertase regulates mechanosensory responses of Caenorhabditis elegans.

Kass J, Jacob TC, Kim P, Kaplan JM

Abstract

Neuroactive peptides are packaged as proproteins into dense core vesicles or secretory granules, where they are cleaved at dibasic residues by copackaged proprotein convertases. We show here that the Caenorhabditis elegans egl-3 gene encodes a protein that is 57% identical to mouse proprotein convertase type 2 (PC2), and we provide evidence that this convertase regulates mechanosensory responses. Nose touch sensitivity (mediated by ASH sensory neurons) is defective in mutants lacking GLR-1 glutamate receptors (GluRs); however, mutations eliminating the egl-3 PC2 restored nose touch sensitivity to glr-1 GluR mutants. By contrast, body touch sensitivity (mediated by the touch cells) is greatly diminished in egl-3 PC2 mutants. Taken together, these results suggest that egl-3 PC2-processed peptides normally regulate the responsiveness of C. elegans to mechanical stimuli.

MeSH Terms
Animals Behavior, Animal/physiology Caenorhabditis elegans/physiology Caenorhabditis elegans Proteins Chromosome Mapping Cloning, Molecular Helminth Proteins/genetics,metabolism Locomotion/physiology Mechanoreceptors/physiology Molecular Sequence Data Mutagenesis, Site-Directed Neurons/physiology Organ Specificity Oviposition/physiology Physical Stimulation Proprotein Convertase 2 Receptors, AMPA Receptors, Glutamate/deficiency,physiology Subtilisins/genetics,metabolism Synapses/physiology Touch/physiology
Chemicals
Caenorhabditis elegans Proteins Helminth Proteins Receptors, AMPA Receptors, Glutamate glr-1 protein, C elegans Subtilisins EGL-3 proprotein convertase, C elegans Proprotein Convertase 2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kass J
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Jacob T C
Kim P
Kaplan J M
References (45)
45 references, click to expand
  1. Effect of a neuropeptide gene on behavioral states in Caenorhabditis elegans egg-laying.
    Genetics. 2000 Mar;154(3):1181-92 PMID: 10757762
  2. G alphas-induced neurodegeneration in Caenorhabditis elegans.
    J Neurosci. 1998 Apr 15;18(8):2871-80 PMID: 9526004
  3. Mechanosensory signalling in C. elegans mediated by the GLR-1 glutamate receptor.
    Nature. 1995 Nov 2;378(6552):78-81 PMID: 7477293
  4. High-throughput isolation of Caenorhabditis elegans deletion mutants.
    Genome Res. 1999 Sep;9(9):859-67 PMID: 10508845
  5. Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2.
    Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6646-51 PMID: 9192619
  6. Cloning and functional analysis of C. elegans 7B2.
    DNA Cell Biol. 1998 Aug;17(8):727-34 PMID: 9726255
  7. EAT-4, a homolog of a mammalian sodium-dependent inorganic phosphate cotransporter, is necessary for glutamatergic neurotransmission in caenorhabditis elegans.
    J Neurosci. 1999 Jan 1;19(1):159-67 PMID: 9870947
  8. Caenorhabditis elegans rab-3 mutant synapses exhibit impaired function and are partially depleted of vesicles.
    J Neurosci. 1997 Nov 1;17(21):8061-73 PMID: 9334382
  9. New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling.
    Genome Res. 1998 Apr;8(4):348-53 PMID: 9548970
  10. Genetic control of differentiation of the Caenorhabditis elegans touch receptor neurons.
    Science. 1989 Feb 24;243(4894 Pt 1):1027-33 PMID: 2646709
  11. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P.
    Nature. 1998 Mar 26;392(6674):394-7 PMID: 9537323
  12. Chemosensory cell function in the behavior and development of Caenorhabditis elegans.
    Cold Spring Harb Symp Quant Biol. 1990;55:529-38 PMID: 2132836
  13. Functional studies of cotransmission.
    Physiol Rev. 1991 Jul;71(3):683-732 PMID: 1647537
  14. The proprotein convertases.
    Curr Opin Chem Biol. 1998 Feb;2(1):31-9 PMID: 9667917
  15. LIN-10 is a shared component of the polarized protein localization pathways in neurons and epithelia.
    Cell. 1998 Sep 18;94(6):751-9 PMID: 9753322
  16. Continuous repetitive stimuli are more effective than bursts for evoking LHRH release in bullfrog sympathetic ganglia.
    J Neurosci. 1991 Jan;11(1):85-95 PMID: 1986070
  17. The neural circuit for touch sensitivity in Caenorhabditis elegans.
    J Neurosci. 1985 Apr;5(4):956-64 PMID: 3981252
  18. Frequency-dependent release of peptide cotransmitters from identified cholinergic motor neurons in Aplysia.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):9034-8 PMID: 2554338
  19. IDA-1, a Caenorhabditis elegans homolog of the diabetic autoantigens IA-2 and phogrin, is expressed in peptidergic neurons in the worm.
    J Comp Neurol. 2001 Jan 1;429(1):127-43 PMID: 11086294
  20. Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans.
    Cell. 1995 Oct 20;83(2):207-18 PMID: 7585938
  21. Mutant sensory cilia in the nematode Caenorhabditis elegans.
    Dev Biol. 1986 Oct;117(2):456-87 PMID: 2428682
  22. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans.
    Cell. 1998 Sep 4;94(5):679-89 PMID: 9741632
  23. Molecular cloning and characterization of a new insulin/IGF-like peptide of the nematode Caenorhabditis elegans.
    Biochem Biophys Res Commun. 2000 Jul 5;273(2):431-6 PMID: 10873623
  24. Disruption of a neuropeptide gene, flp-1, causes multiple behavioral defects in Caenorhabditis elegans.
    Science. 1998 Sep 11;281(5383):1686-90 PMID: 9733518
  25. Localization of FMRFamide-like peptides in Caenorhabditis elegans.
    J Comp Neurol. 1992 Feb 8;316(2):251-60 PMID: 1573054
  26. Peripheral and spinal mechanisms of nociception.
    Physiol Rev. 1987 Jan;67(1):67-186 PMID: 3543978
  27. Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family.
    Genes Dev. 2001 Mar 15;15(6):672-86 PMID: 11274053
  28. A role for amontillado, the Drosophila homolog of the neuropeptide precursor processing protease PC2, in triggering hatching behavior.
    J Neurosci. 1999 Aug 15;19(16):6942-54 PMID: 10436051
  29. Cloning and developmental regulation of a novel member of the insulin-like gene family in Caenorhabditis elegans.
    Biochem Biophys Res Commun. 1998 Aug 19;249(2):385-90 PMID: 9712706
  30. A dual mechanosensory and chemosensory neuron in Caenorhabditis elegans.
    Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2227-31 PMID: 8460126
  31. Isolation and in situ localization of a cDNA encoding a Kex2-like prohormone convertase in the nematode Caenorhabditis elegans.
    Cell Mol Neurobiol. 1994 Feb;14(1):9-25 PMID: 7954663
  32. Muscle and nerve-specific regulation of a novel NK-2 class homeodomain factor in Caenorhabditis elegans.
    Development. 1998 Feb;125(3):421-9 PMID: 9425137
  33. Primary afferent tachykinins are required to experience moderate to intense pain.
    Nature. 1998 Mar 26;392(6674):390-4 PMID: 9537322
  34. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene.
    Nat Genet. 1997 Jul;16(3):303-6 PMID: 9207799
  35. Integration of mechanosensory stimuli in Caenorhabditis elegans.
    J Neurosci. 1995 Mar;15(3 Pt 2):2434-44 PMID: 7891178
  36. Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter.
    Science. 2000 Aug 11;289(5481):957-60 PMID: 10938000
  37. Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons.
    Nature. 2000 Sep 14;407(6801):189-94 PMID: 11001057
  38. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans.
    Science. 1997 Aug 15;277(5328):942-6 PMID: 9252323
  39. Synaptic code for sensory modalities revealed by C. elegans GLR-1 glutamate receptor.
    Nature. 1995 Nov 2;378(6552):82-5 PMID: 7477294
  40. Egg-laying defective mutants of the nematode Caenorhabditis elegans.
    Genetics. 1983 Aug;104(4):619-47 PMID: 11813735
  41. Neuropeptide gene families in the nematode Caenorhabditis elegans.
    Ann N Y Acad Sci. 1999;897:239-52 PMID: 10676452
  42. A dynamic network simulation of the nematode tap withdrawal circuit: predictions concerning synaptic function using behavioral criteria.
    J Neurosci. 1996 Jun 15;16(12):4017-31 PMID: 8656295
  43. The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing's disease.
    Cell. 1999 Mar 5;96(5):689-700 PMID: 10089884
  44. Distinct signaling pathways mediate touch and osmosensory responses in a polymodal sensory neuron.
    J Neurosci. 1999 Mar 15;19(6):1952-8 PMID: 10066248
  45. Molecular and cellular regulation of prohormone processing.
    Semin Cell Dev Biol. 1998 Feb;9(1):3-10 PMID: 9572108
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-12-01
Pages
9265-72
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6763909
Subset
IM
Grants
NINDS NIH HHS · NS32196 · United States
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