NDLI: Role of G-Substrate in the NO/cGMP/PKG Signal Transduction Pathway for Photic Entrainment of the Hamster Circadian Clock

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Role of G-Substrate in the NO/cGMP/PKG Signal Transduction Pathway for Photic Entrainment of the Hamster Circadian Clock

Content Provider	SAGE Publishing
Author	Plano, Santiago Andrés Alessandro, María Soledad Trebucq, Laura Lucía Endo, Shogo Golombek, Diego Andrés Chiesa, Juan José
Copyright Year	2021
Abstract	The mammalian circadian clock at the hypothalamic suprachiasmatic nuclei (SCN) entrains biological rhythms to the 24-h cyclic environment, by encoding light-dark transitions in SCN neurons. Light pulses induce phase shifts in the clock and in circadian rhythms; photic signaling for circadian phase advances involves a nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) pathway, increasing the expression of Period (Per) genes. Effectors downstream of PKG remain unknown. Here we investigate the role of G-substrate (GS), a PKG substrate, in the hamster SCN. GS and phosphorylated G-substrate (p-GS) were present in a subset of SCN cells. Moreover, GS phosphorylation (p-GS/GS ratio) increased in SCN homogenates after light pulses delivered at circadian time (CT) 18 and intraperitoneal treatment with sildenafil, an inhibitor of phosphodiesterase 5 (a cGMP-specific phosphodiesterase). On the other hand, intracerebroventricular treatment with the PKG inhibitor KT5823, reduced photic phosphorylation of GS to basal levels. Since p-GS could act as a protein phosphatase 2 A (PP2A) inhibitor, we demonstrated physical interaction between p-GS and PP2A in SCN homogenates, and also a light-pulse dependent decrease of PP2A activity. Intracerebroventricular treatment with okadaic acid, a PP2A inhibitor, increased the magnitude of light-induced phase advances of locomotor rhythms. We provide evidence on the physiological phosphorylation of GS as a new downstream effector in the NO/cGMP/PKG photic pathway in the hamster SCN, including its role as a PP2A inhibitor.
Related Links	https://journals.sagepub.com/doi/pdf/10.1177/1759091420984920?download=true
ISSN	17590914
Volume Number	13
Journal	ASN Neuro (ASN)
e-ISSN	17590914
DOI	10.1177/1759091420984920
Language	English
Publisher	Sage Publications CA
Publisher Date	2021-01-11
Publisher Place	Los Angeles
Access Restriction	Open
Rights Holder	© The Author(s) 2021
Subject Keyword	protein phosphatase 2A phase advance G-substrate suprachiasmatic nuclei
Content Type	Text
Resource Type	Article
Subject	Neuroscience Neurology (clinical)

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