Cargando…

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

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 b...

Descripción completa

Detalles Bibliográficos
Autores principales: Ashlin, Tim G., Blunsom, Nicholas J., Ghosh, Marcus, Cockcroft, Shamshad, Rihel, Jason
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092267/
https://www.ncbi.nlm.nih.gov/pubmed/30089250
http://dx.doi.org/10.1016/j.celrep.2018.07.012
_version_ 1783347494835453952
author Ashlin, Tim G.
Blunsom, Nicholas J.
Ghosh, Marcus
Cockcroft, Shamshad
Rihel, Jason
author_facet Ashlin, Tim G.
Blunsom, Nicholas J.
Ghosh, Marcus
Cockcroft, Shamshad
Rihel, Jason
author_sort Ashlin, Tim G.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6092267
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Cell Press
record_format MEDLINE/PubMed
spelling pubmed-60922672018-08-15 Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling Ashlin, Tim G. Blunsom, Nicholas J. Ghosh, Marcus Cockcroft, Shamshad Rihel, Jason Cell Rep Article 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. Cell Press 2018-08-07 /pmc/articles/PMC6092267/ /pubmed/30089250 http://dx.doi.org/10.1016/j.celrep.2018.07.012 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ashlin, Tim G.
Blunsom, Nicholas J.
Ghosh, Marcus
Cockcroft, Shamshad
Rihel, Jason
Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling
title Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling
title_full Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling
title_fullStr Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling
title_full_unstemmed Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling
title_short Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling
title_sort pitpnc1a regulates zebrafish sleep and wake behavior through modulation of insulin-like growth factor signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092267/
https://www.ncbi.nlm.nih.gov/pubmed/30089250
http://dx.doi.org/10.1016/j.celrep.2018.07.012
work_keys_str_mv AT ashlintimg pitpnc1aregulateszebrafishsleepandwakebehaviorthroughmodulationofinsulinlikegrowthfactorsignaling
AT blunsomnicholasj pitpnc1aregulateszebrafishsleepandwakebehaviorthroughmodulationofinsulinlikegrowthfactorsignaling
AT ghoshmarcus pitpnc1aregulateszebrafishsleepandwakebehaviorthroughmodulationofinsulinlikegrowthfactorsignaling
AT cockcroftshamshad pitpnc1aregulateszebrafishsleepandwakebehaviorthroughmodulationofinsulinlikegrowthfactorsignaling
AT riheljason pitpnc1aregulateszebrafishsleepandwakebehaviorthroughmodulationofinsulinlikegrowthfactorsignaling