Journal article
Patched 1 reduces the accessibility of cholesterol in the outer leaflet of membranes
- Abstract:
- Cells coordinate nearly countless numbers of signaling reactions within them at any given time. To distinguish between different signaling inputs and outputs, cells utilize spatially compartmentalized signaling hubs to regulate their biochemical processes. We review how the primary cilium, an organelle specialized in intracellular signaling, utilizes lipids to create a specialized microenvironment. Hedgehog (HH) signaling in vertebrates is dependent on the primary cilium, an organelle that scaffolds signal transduction. HH signals induce Smoothened (SMO) enrichment in the cilium and indirectly triggers the conversion of GLI proteins into transcriptional activators of HH target genes. Recently, SMO has been shown to inhibit protein kinase A (PKA). To test the hypothesis that SMO specifically inhibits PKA at cilia to activate the HH signal transduction pathway, we developed a ciliary PKA biosensor. Activation of the HH signal transduction pathway by either Sonic hedgehog (SHH) or SMO agonist (SAG) inhibited ciliary PKA activity. Blocking SMO phosphorylation by GRK2/3 prevented ciliary SMO from inhibiting ciliary PKA activity. Gai/o was dispensable for SMO inhibition of ciliary PKA. In contrast, mutating the SMO C-terminal tail protein kinase inhibitor (PKI) pseudosubstrate site interfered with the ability of SMO to inhibit ciliary PKA. Therefore, HH signaling is transduced via SMO direct inhibition of PKA at cilia, in a manner dependent on GRK2/3
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Version of record, plain, 2.0KB, Terms of use)
-
- Publisher copy:
- 10.7554/elife.70504
- Publication website:
- https://escholarship.org/content/qt0gt9v55z/qt0gt9v55z.pdf
Authors
+ Ford Foundation
More from this funder
- Funder identifier:
- 10.13039/100000010
- Grant:
- Predoctoral Fellowship
+ National Science Foundation
More from this funder
- Funder identifier:
- 10.13039/100000001
- Grant:
- Predoctoral Fellowship
+ Ministry of Education, Singapore
More from this funder
- Funder identifier:
- 10.13039/501100001459
- Grant:
- MOE2017-T2-2-001
- Publisher:
- eLife Sciences Publications
- Journal:
- eLife More from this journal
- Volume:
- 10
- Pages:
- e70504
- Article number:
- e70504
- Publication date:
- 2021-10-26
- Acceptance date:
- 2021-10-25
- DOI:
- EISSN:
-
2050-084X
- ISSN:
-
2050-084X
- Language:
-
English
- Keywords:
- Pubs id:
-
1211099
- Local pid:
-
pubs:1211099
- Source identifiers:
-
W3209305865
- Deposit date:
-
2026-04-08
- ARK identifier:
This ORA record was generated from metadata provided by an external service. It has not been edited by the ORA Team.
Terms of use
- Copyright date:
- 2021
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record