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Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling

Ashlin, TG; Blunsom, NJ; Ghosh, M; Cockcroft, S; Rihel, J; (2018) Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling. Cell Reports , 24 (6) pp. 1389-1396. 10.1016/j.celrep.2018.07.012. Green open access

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Abstract

The lipid transporters of the phosphatidylinositol transfer protein (PITP) family dictate phosphoinositide compartmentalization, and specific phosphoinositides play crucial roles in signaling cascades, membrane traffic, ion channel regulation, and actin dynamics. Although PITPs are enriched in the brain, their physiological functions in neuronal signaling pathways in vivo remain ill defined. We describe a CRISPR/Cas9-generated zebrafish mutant in a brain-specific, conserved class II PITP member, pitpnc1a. Zebrafish pitpnc1a mutants are healthy but display widespread aberrant neuronal activity and increased wakefulness across the day-night cycle. The loss of Pitpnc1a increases insulin-like growth factor (IGF) signaling in the brain, and inhibition of IGF pathways is sufficient to rescue both neuronal and behavioral hyperactivity in pitpnc1a mutants. We propose that Pitpnc1a-expressing neurons alter behavior via modification of neuro-modulatory IGF that acts on downstream wake-promoting circuits.

Type: Article
Title: Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2018.07.012
Publisher version: https://doi.org/10.1016/j.celrep.2018.07.012
Language: English
Additional information: © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: zebrafish, sleep, lipid transporter, behavior, IGF
URI: http://discovery.ucl.ac.uk/id/eprint/10054175
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