NDLI: Cilia have high cAMP levels that are inhibited by Sonic Hedgehog-regulated calcium dynamics.

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Cilia have high cAMP levels that are inhibited by Sonic Hedgehog-regulated calcium dynamics.

Content Provider	Semantic Scholar
Author	Stepanchick, Ann N. Zhang, Jin Quinn, Anne Marie Hughes, Thomas E. Mirshahi, Tooraj
Copyright Year	2016
Abstract	Protein kinase A (PKA) phosphorylates Gli proteins, acting as a negative regulator of the Hedgehog pathway. PKA was recently detected within the cilium, and PKA activity specifically in cilia regulates Gli processing. Using a cilia-targeted genetically encoded sensor, we found significant basal PKA activity. Using another targeted sensor, we measured basal ciliary cAMP that is fivefold higher than whole-cell cAMP. The elevated basal ciliary cAMP level is a result of adenylyl cyclase 5 and 6 activity that depends on ciliary phosphatidylinositol (3,4,5)-trisphosphate (PIP3), not stimulatory G protein (Gαs), signaling. Sonic Hedgehog (SHH) reduces ciliary cAMP levels, inhibits ciliary PKA activity, and increases Gli1. Remarkably, SHH regulation of ciliary cAMP and downstream signals is not dependent on inhibitory G protein (Gαi/o) signaling but rather Ca2+ entry through a Gd3+-sensitive channel. Therefore, PIP3 sustains high basal cAMP that maintains PKA activity in cilia and Gli repression. SHH activates Gli by inhibiting cAMP through a G protein-independent mechanism that requires extracellular Ca2+ entry.
Starting Page	13069
Ending Page	13074
Page Count	6
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.pnas.org/content/113/46/13069.full.pdf
PubMed reference number	27799542v1
Volume Number	113
Issue Number	46
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Subject Keyword	8-chloro-cyclic adenosine monophosphate Adenylate Cyclase Basal Ganglia Diseases Calcium ion Cilia Cyclic AMP-Dependent Protein Kinases GLI1 protein, human Inhibition Proximal Interphalangeal Joint 3 Repression, Psychology SHH gene SHH protein, human
Content Type	Text
Resource Type	Article

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