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The Caenorhabditis elegans cysteine-string protein homologue DNJ-14 is dispensable for neuromuscular junction maintenance across ageing

The Caenorhabditis elegans cysteine-string protein homologue DNJ-14 is dispensable for neuromuscular junction maintenance across ageing
The Caenorhabditis elegans cysteine-string protein homologue DNJ-14 is dispensable for neuromuscular junction maintenance across ageing
Maintenance of synaptic function across ageing is vital in sustaining cognitive function. Synaptic dysfunction is a key part of the pathophysiology of a number of neurodegenerative diseases. The synaptic co-chaperone, cysteine-string protein (CSP), is important for synaptic maintenance and function in Drosophila, mice and humans, and disruption of CSP results in synaptic degeneration. We sought to characterise synaptic ageing in Caenorhabditis elegans upon genetic disruption of CSP. To do this, we focused on the worms' neuromuscular junctions, which are the best characterised synapse. CSP mutant worms did not display reduced lifespan or any neuromuscular-dependent behavioural deficits across ageing. Pharmacological interrogation of the neuromuscular synapse of CSP mutant animals showed no sign of synaptic dysfunction even at advanced age. Lastly, patch clamp analysis of neuromuscular transmission across ageing in wild-type and CSP mutant animals revealed no obvious CSP-dependent deficits. Electrophysiological spontaneous postsynaptic current analysis reinforced pharmacological observations that the C. elegans neuromuscular synapse increases in strength during early ageing and remains relatively intact in old, immotile worms. Taken together, this study shows that surprisingly, despite disruption of CSP in other animals having severe synaptic phenotypes, CSP does not seem to be important for maintenance of the neuromuscular junction across ageing in C. elegans.
0022-0949
1-8
Mulcahy, Ben
9f49ae09-3cb2-4335-b4e2-225d0974d628
Ibbett, Paul
bac07548-e35f-4f01-89c1-71b3404aa4e4
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
O'connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Mulcahy, Ben
9f49ae09-3cb2-4335-b4e2-225d0974d628
Ibbett, Paul
bac07548-e35f-4f01-89c1-71b3404aa4e4
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
O'connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca

Mulcahy, Ben, Ibbett, Paul, Holden-Dye, Lindy and O'connor, Vincent (2019) The Caenorhabditis elegans cysteine-string protein homologue DNJ-14 is dispensable for neuromuscular junction maintenance across ageing. Journal of Experimental Biology, 222 (22), 1-8, [jeb205450]. (doi:10.1242/jeb.205450).

Record type: Article

Abstract

Maintenance of synaptic function across ageing is vital in sustaining cognitive function. Synaptic dysfunction is a key part of the pathophysiology of a number of neurodegenerative diseases. The synaptic co-chaperone, cysteine-string protein (CSP), is important for synaptic maintenance and function in Drosophila, mice and humans, and disruption of CSP results in synaptic degeneration. We sought to characterise synaptic ageing in Caenorhabditis elegans upon genetic disruption of CSP. To do this, we focused on the worms' neuromuscular junctions, which are the best characterised synapse. CSP mutant worms did not display reduced lifespan or any neuromuscular-dependent behavioural deficits across ageing. Pharmacological interrogation of the neuromuscular synapse of CSP mutant animals showed no sign of synaptic dysfunction even at advanced age. Lastly, patch clamp analysis of neuromuscular transmission across ageing in wild-type and CSP mutant animals revealed no obvious CSP-dependent deficits. Electrophysiological spontaneous postsynaptic current analysis reinforced pharmacological observations that the C. elegans neuromuscular synapse increases in strength during early ageing and remains relatively intact in old, immotile worms. Taken together, this study shows that surprisingly, despite disruption of CSP in other animals having severe synaptic phenotypes, CSP does not seem to be important for maintenance of the neuromuscular junction across ageing in C. elegans.

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More information

Accepted/In Press date: 9 October 2019
e-pub ahead of print date: 17 October 2019
Published date: 25 November 2019

Identifiers

Local EPrints ID: 437775
URI: http://eprints.soton.ac.uk/id/eprint/437775
ISSN: 0022-0949
PURE UUID: 7dab5fd9-a51c-4bcb-8c8d-972620ef643e
ORCID for Lindy Holden-Dye: ORCID iD orcid.org/0000-0002-9704-1217

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Date deposited: 14 Feb 2020 17:33
Last modified: 18 Feb 2021 16:34

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Contributors

Author: Ben Mulcahy
Author: Paul Ibbett

University divisions

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