RRC ID 66066
Author Meserve JH, Nelson JC, Marsden KC, Hsu J, Echeverry FA, Jain RA, Wolman MA, Pereda AE, Granato M.
Title A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.
Journal PLoS Genet
Abstract 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.
Volume 17(6)
Pages e1008943
Published 2021-6-1
DOI 10.1371/journal.pgen.1008943
PMID 34061829
PMC PMC8195410
MeSH Animals Genetic Testing / methods* Humans Kv1.1 Potassium Channel / genetics* Phosphotransferases (Alcohol Group Acceptor) / genetics Phosphotransferases (Alcohol Group Acceptor) / physiology* Reflex, Startle / genetics* Zebrafish Zebrafish Proteins / genetics*
IF 5.175
Zebrafish Tol-056 Tg(chx10:Gal4) hspGFF62A