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

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Ashlin TG,Blunsom NJ,Ghosh M,Cockcroft S,Rihel J

doi

10.1016/j.celrep.2018.07.012

subject

Has Abstract

pub_date

2018-08-07 00:00:00

pages

1389-1396

issue

6

issn

2211-1247

pii

S2211-1247(18)31089-1

journal_volume

24

pub_type

杂志文章

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