A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.

The acoustic startle response is an evolutionarily conserved avoidance behavior. Disruptions in startle behavior, particularly startle magnitude, are a hallmark of several human neurological disorders. While the neural circuitry underlying startle behavior has been studied extensively, the repertoir...

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Autores principales:	Joy H Meserve, Jessica C Nelson, Kurt C Marsden, Jerry Hsu, Fabio A Echeverry, Roshan A Jain, Marc A Wolman, Alberto E Pereda, Michael Granato
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/66523a4c7fc74299ad1b74824cdd69a7
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spelling	oai:doaj.org-article:66523a4c7fc74299ad1b74824cdd69a72021-12-02T20:02:43ZA forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.1553-73901553-740410.1371/journal.pgen.1008943https://doaj.org/article/66523a4c7fc74299ad1b74824cdd69a72021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1008943https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404The acoustic startle response is an evolutionarily conserved avoidance behavior. Disruptions in startle behavior, particularly startle magnitude, are a hallmark of several human neurological disorders. While the neural circuitry underlying startle behavior has been studied extensively, the repertoire of genes and genetic pathways that regulate this locomotor behavior has not been explored using an unbiased genetic approach. To identify such genes, we took advantage of the stereotypic startle behavior in zebrafish larvae and performed a forward genetic screen coupled with whole genome analysis. We uncovered mutations in eight genes critical for startle behavior, including two genes encoding proteins associated with human neurological disorders, Dolichol kinase (Dolk), a broadly expressed regulator of the glycoprotein biosynthesis pathway, and the potassium Shaker-like channel subunit Kv1.1. We demonstrate that Kv1.1 and Dolk play critical roles in the spinal cord to regulate movement magnitude during the startle response and spontaneous swim movements. Moreover, we show that Kv1.1 protein is mislocalized in dolk mutants, suggesting they act in a common genetic pathway. Combined, our results identify a diverse set of eight genes, all associated with human disorders, that regulate zebrafish startle behavior and reveal a previously unappreciated role for Dolk and Kv1.1 in regulating movement magnitude via a common genetic pathway.Joy H MeserveJessica C NelsonKurt C MarsdenJerry HsuFabio A EcheverryRoshan A JainMarc A WolmanAlberto E PeredaMichael GranatoPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 6, p e1008943 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Joy H Meserve Jessica C Nelson Kurt C Marsden Jerry Hsu Fabio A Echeverry Roshan A Jain Marc A Wolman Alberto E Pereda Michael Granato A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.
description	The acoustic startle response is an evolutionarily conserved avoidance behavior. Disruptions in startle behavior, particularly startle magnitude, are a hallmark of several human neurological disorders. While the neural circuitry underlying startle behavior has been studied extensively, the repertoire of genes and genetic pathways that regulate this locomotor behavior has not been explored using an unbiased genetic approach. To identify such genes, we took advantage of the stereotypic startle behavior in zebrafish larvae and performed a forward genetic screen coupled with whole genome analysis. We uncovered mutations in eight genes critical for startle behavior, including two genes encoding proteins associated with human neurological disorders, Dolichol kinase (Dolk), a broadly expressed regulator of the glycoprotein biosynthesis pathway, and the potassium Shaker-like channel subunit Kv1.1. We demonstrate that Kv1.1 and Dolk play critical roles in the spinal cord to regulate movement magnitude during the startle response and spontaneous swim movements. Moreover, we show that Kv1.1 protein is mislocalized in dolk mutants, suggesting they act in a common genetic pathway. Combined, our results identify a diverse set of eight genes, all associated with human disorders, that regulate zebrafish startle behavior and reveal a previously unappreciated role for Dolk and Kv1.1 in regulating movement magnitude via a common genetic pathway.
format	article
author	Joy H Meserve Jessica C Nelson Kurt C Marsden Jerry Hsu Fabio A Echeverry Roshan A Jain Marc A Wolman Alberto E Pereda Michael Granato
author_facet	Joy H Meserve Jessica C Nelson Kurt C Marsden Jerry Hsu Fabio A Echeverry Roshan A Jain Marc A Wolman Alberto E Pereda Michael Granato
author_sort	Joy H Meserve
title	A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.
title_short	A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.
title_full	A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.
title_fullStr	A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.
title_full_unstemmed	A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.
title_sort	forward genetic screen identifies dolk as a regulator of startle magnitude through the potassium channel subunit kv1.1.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/66523a4c7fc74299ad1b74824cdd69a7
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A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.

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