rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.

Injured axons must regenerate to restore nervous system function, and regeneration is regulated in part by external factors from non-neuronal tissues. Many of these extrinsic factors act in the immediate cellular environment of the axon to promote or restrict regeneration, but the existence of long-...

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Autores principales:	Alexander T Lin-Moore, Motunrayo J Oyeyemi, Marc Hammarlund
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/ccaffbe9ffaf44b0bdd1135d7788c8e6
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spelling	oai:doaj.org-article:ccaffbe9ffaf44b0bdd1135d7788c8e62021-12-02T20:03:26Zrab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.1553-73901553-740410.1371/journal.pgen.1009877https://doaj.org/article/ccaffbe9ffaf44b0bdd1135d7788c8e62021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009877https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Injured axons must regenerate to restore nervous system function, and regeneration is regulated in part by external factors from non-neuronal tissues. Many of these extrinsic factors act in the immediate cellular environment of the axon to promote or restrict regeneration, but the existence of long-distance signals regulating axon regeneration has not been clear. Here we show that the Rab GTPase rab-27 inhibits regeneration of GABAergic motor neurons in C. elegans through activity in the intestine. Re-expression of RAB-27, but not the closely related RAB-3, in the intestine of rab-27 mutant animals is sufficient to rescue normal regeneration. Several additional components of an intestinal neuropeptide secretion pathway also inhibit axon regeneration, including NPDC1/cab-1, SNAP25/aex-4, KPC3/aex-5, and the neuropeptide NLP-40, and re-expression of these genes in the intestine of mutant animals is sufficient to restore normal regeneration success. Additionally, NPDC1/cab-1 and SNAP25/aex-4 genetically interact with rab-27 in the context of axon regeneration inhibition. Together these data indicate that RAB-27-dependent neuropeptide secretion from the intestine inhibits axon regeneration, and point to distal tissues as potent extrinsic regulators of regeneration.Alexander T Lin-MooreMotunrayo J OyeyemiMarc HammarlundPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 11, p e1009877 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Alexander T Lin-Moore Motunrayo J Oyeyemi Marc Hammarlund rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.
description	Injured axons must regenerate to restore nervous system function, and regeneration is regulated in part by external factors from non-neuronal tissues. Many of these extrinsic factors act in the immediate cellular environment of the axon to promote or restrict regeneration, but the existence of long-distance signals regulating axon regeneration has not been clear. Here we show that the Rab GTPase rab-27 inhibits regeneration of GABAergic motor neurons in C. elegans through activity in the intestine. Re-expression of RAB-27, but not the closely related RAB-3, in the intestine of rab-27 mutant animals is sufficient to rescue normal regeneration. Several additional components of an intestinal neuropeptide secretion pathway also inhibit axon regeneration, including NPDC1/cab-1, SNAP25/aex-4, KPC3/aex-5, and the neuropeptide NLP-40, and re-expression of these genes in the intestine of mutant animals is sufficient to restore normal regeneration success. Additionally, NPDC1/cab-1 and SNAP25/aex-4 genetically interact with rab-27 in the context of axon regeneration inhibition. Together these data indicate that RAB-27-dependent neuropeptide secretion from the intestine inhibits axon regeneration, and point to distal tissues as potent extrinsic regulators of regeneration.
format	article
author	Alexander T Lin-Moore Motunrayo J Oyeyemi Marc Hammarlund
author_facet	Alexander T Lin-Moore Motunrayo J Oyeyemi Marc Hammarlund
author_sort	Alexander T Lin-Moore
title	rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.
title_short	rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.
title_full	rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.
title_fullStr	rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.
title_full_unstemmed	rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.
title_sort	rab-27 acts in an intestinal pathway to inhibit axon regeneration in c. elegans.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ccaffbe9ffaf44b0bdd1135d7788c8e6
work_keys_str_mv	AT alexandertlinmoore rab27actsinanintestinalpathwaytoinhibitaxonregenerationincelegans AT motunrayojoyeyemi rab27actsinanintestinalpathwaytoinhibitaxonregenerationincelegans AT marchammarlund rab27actsinanintestinalpathwaytoinhibitaxonregenerationincelegans
_version_	1718375687587364864

rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans.

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