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Caenorhabditis elegans Neprilysin nep-1: An effector of locomotion and pharyngeal pumping

Caenorhabditis elegans Neprilysin nep-1: An effector of locomotion and pharyngeal pumping
Caenorhabditis elegans Neprilysin nep-1: An effector of locomotion and pharyngeal pumping
The control of signal peptide activity by cell surface proteases is one of the main factors that regulate the development and behaviour of organisms. In mammals, neprilysins (NEPs) are known to play a key role in these processes and their inactivation can initiate cellular disorganisation, which in turn may lead to prostate cancer or Hirschsprung disease. Although the proteome of the nematode Caenorhabditis elegans has been intensively studied, very little is known about the function of neprilysins. ZK20.6 (NEP-1), the C. elegans protein with highest identity to mammalian neprilysins, is a 753 amino acid residue protein that displays all neprilysin-typical characteristics, including a short intracellular domain, a transmembrane domain and a long extracellular active domain. Here we show that the expression pattern of nep-1 is limited to pharyngeal cells and a single head neuron. Compared to wild-type, the locomotion of nep-1 knockout animals is significantly impaired, a phenotype that can be rescued by the extrachromosomal re-introduction of nep-1. This suggests that this enzyme plays an important role in the regulation of nematode locomotion. Finally, electrophysiological recording of the pharyngeal activity showed a high sensitivity of the nep-1 pharynx to serotonin (5-HT) and to the neuropeptide AF1 (C. elegans FLP-8), indicating that NEP-1 is a central component that controls the neuronal innervation of pharyngeal pumping in C. elegans.
Caenorhabditis elegans, neuropeptide, motility, serotonin, electrophysiology
0022-2836
429-437
Spanier, B.
44baae23-8137-4029-ab11-f2dae7107b83
Sturzenbaum, S.R.
7f6bbaf7-c2c3-44ed-9ed8-ad85390a02cb
Holden-Dye, L.M.
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Baumeister, R.
e797b745-e7d8-498c-8516-d9a9f2a76da0
Spanier, B.
44baae23-8137-4029-ab11-f2dae7107b83
Sturzenbaum, S.R.
7f6bbaf7-c2c3-44ed-9ed8-ad85390a02cb
Holden-Dye, L.M.
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Baumeister, R.
e797b745-e7d8-498c-8516-d9a9f2a76da0

Spanier, B., Sturzenbaum, S.R., Holden-Dye, L.M. and Baumeister, R. (2005) Caenorhabditis elegans Neprilysin nep-1: An effector of locomotion and pharyngeal pumping. Journal of Molecular Biology, 352 (2), 429-437. (doi:10.1016/j.jmb.2005.06.063).

Record type: Article

Abstract

The control of signal peptide activity by cell surface proteases is one of the main factors that regulate the development and behaviour of organisms. In mammals, neprilysins (NEPs) are known to play a key role in these processes and their inactivation can initiate cellular disorganisation, which in turn may lead to prostate cancer or Hirschsprung disease. Although the proteome of the nematode Caenorhabditis elegans has been intensively studied, very little is known about the function of neprilysins. ZK20.6 (NEP-1), the C. elegans protein with highest identity to mammalian neprilysins, is a 753 amino acid residue protein that displays all neprilysin-typical characteristics, including a short intracellular domain, a transmembrane domain and a long extracellular active domain. Here we show that the expression pattern of nep-1 is limited to pharyngeal cells and a single head neuron. Compared to wild-type, the locomotion of nep-1 knockout animals is significantly impaired, a phenotype that can be rescued by the extrachromosomal re-introduction of nep-1. This suggests that this enzyme plays an important role in the regulation of nematode locomotion. Finally, electrophysiological recording of the pharyngeal activity showed a high sensitivity of the nep-1 pharynx to serotonin (5-HT) and to the neuropeptide AF1 (C. elegans FLP-8), indicating that NEP-1 is a central component that controls the neuronal innervation of pharyngeal pumping in C. elegans.

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More information

Submitted date: 13 May 2005
Published date: 1 September 2005
Keywords: Caenorhabditis elegans, neuropeptide, motility, serotonin, electrophysiology

Identifiers

Local EPrints ID: 55975
URI: https://eprints.soton.ac.uk/id/eprint/55975
ISSN: 0022-2836
PURE UUID: 7147634a-1d0e-44be-9e9a-7a44decb5109

Catalogue record

Date deposited: 08 Aug 2008
Last modified: 13 Mar 2019 20:35

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