We have isolated and sequenced a large family of 20 novel endogenous neuropeptides in the nematode, Ascaris suum. Preliminary experiments have shown that each of the peptides tested so far has potent activity on the neuromuscular system of Ascaris. Some causes paralysis, others exaggerate locomotory movements. Different peptides affect the physiological properties of different neurons in the motornervous system in a variety of ways. The peptides fall into at least 4 subfamilies based on their amino acid sequences. We have shown that one of these subfamilies, comprising 6 peptides, is derived from a precursor protein encoded by a single mRNA coding sequence, strongly reinforcing the concept of subfamilies. Our long-term aim is to understand the role of these peptides in the control of locomotion in Ascaris. In this proposal we plan to use electrophysiological techniques to characterize the signalling pathways mediated by each peptide, and to use molecular biological techniques to determine the genetic organization of this family of peptides. Our hypothesis is that there is a direct correspondence between the subfamilies of peptides defined three ways: by amino acid sequence, by physiological action, and by co-expression on a transcript. We predict that subfamilies exist because each subfamily is the product of a distinct transcript that organizes the co-expression of peptides having similar biological activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI015429-18
Application #
2633422
Study Section
Special Emphasis Panel (ZRG5-TMP (04))
Project Start
1979-01-01
Project End
2000-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
18
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Konop, Christopher J; Knickelbine, Jennifer J; Sygulla, Molly S et al. (2015) Mass Spectrometry of Single GABAergic Somatic Motorneurons Identifies a Novel Inhibitory Peptide, As-NLP-22, in the Nematode Ascaris suum. J Am Soc Mass Spectrom 26:2009-23
Konop, Christopher J; Knickelbine, Jennifer J; Sygulla, Molly S et al. (2015) Different neuropeptides are expressed in different functional subsets of cholinergic excitatory motorneurons in the nematode Ascaris suum. ACS Chem Neurosci 6:855-70
Jarecki, Jessica L; Viola, India R; Andersen, Kari M et al. (2013) Three independent techniques localize expression of transcript afp-11 and its bioactive peptide products to the paired AVK neurons in Ascaris suum: in situ hybridization, immunocytochemistry, and single cell mass spectrometry. ACS Chem Neurosci 4:418-34
Reinitz, Catharine A; Pleva, Anthony E; Stretton, Antony O W (2011) Changes in cyclic nucleotides, locomotory behavior, and body length produced by novel endogenous neuropeptides in the parasitic nematode Ascaris suum. Mol Biochem Parasitol 180:27-34
Jarecki, Jessica L; Frey, Brian L; Smith, Lloyd M et al. (2011) Discovery of neuropeptides in the nematode Ascaris suum by database mining and tandem mass spectrometry. J Proteome Res 10:3098-106
Sithigorngul, Paisarn; Jarecki, Jessica L; Stretton, Antony O W (2011) A specific antibody to neuropeptide AF1 (KNEFIRFamide) recognizes a small subset of neurons in Ascaris suum: differences from Caenorhabditis elegans. J Comp Neurol 519:1546-61
Jarecki, Jessica L; Andersen, Kari; Konop, Christopher J et al. (2010) Mapping neuropeptide expression by mass spectrometry in single dissected identified neurons from the dorsal ganglion of the nematode Ascaris suum. ACS Chem Neurosci 1:505-519
Nanda, Jennifer Cho; Stretton, Antony O W (2010) In situ hybridization of neuropeptide-encoding transcripts afp-1, afp-3, and afp-4 in neurons of the nematode Ascaris suum. J Comp Neurol 518:896-910
Yew, Joanne Y; Davis, Ralph; Dikler, Sergei et al. (2007) Peptide products of the afp-6 gene of the nematode Ascaris suum have different biological actions. J Comp Neurol 502:872-82
McKenna, Philip M; Koser, Martin L; Carlson, Kevin R et al. (2007) Highly attenuated rabies virus-based vaccine vectors expressing simian-human immunodeficiency virus89.6P Env and simian immunodeficiency virusmac239 Gag are safe in rhesus macaques and protect from an AIDS-like disease. J Infect Dis 195:980-8

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