Plexins promote Hedgehog signaling through their cytoplasmic GAP activity
dc.contributor.author | Pinskey, JM | |
dc.contributor.author | Hoard, TM | |
dc.contributor.author | Zhao, XF | |
dc.contributor.author | Franks, NE | |
dc.contributor.author | Frank, ZC | |
dc.contributor.author | McMellen, AN | |
dc.contributor.author | Giger, RJ | |
dc.contributor.author | Allen, BL | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-05-21T15:16:55Z | |
dc.date.available | 2024-05-21T15:16:55Z | |
dc.date.issued | 2022-09-01 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/36169302 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/193168 | en |
dc.description.abstract | Hedgehog signaling controls tissue patterning during embryonic and postnatal development and continues to play important roles throughout life. Characterizing the full comple-ment of Hedgehog pathway components is essential to understanding its wide-ranging functions. Previous work has identified neuropilins, established semaphorin receptors, as positive regulators of Hedgehog signaling. Neuropilins require plexin co-receptors to mediate semaphorin signaling, but the role of plexins in Hedgehog signaling has not yet been explored. Here, we provide evidence that multiple plexins promote Hedgehog signaling in NIH/3T3 mouse fibroblasts and that plexin loss of function in these cells results in significantly reduced Hedgehog pathway activity. Catalytic activity of the plexin GTPase-activating protein (GAP) domain is required for Hedgehog signal promotion, and constitutive activation of the GAP domain further amplifies Hedgehog signaling. Additionally, we demonstrate that plexins promote Hedgehog signaling at the level of GLI transcription factors and that this promotion requires intact primary cilia. Finally, we find that plexin loss of function significantly reduces the response to Hedgehog pathway activation in the mouse dentate gyrus. Together, these data identify plexins as novel components of the Hedgehog pathway and provide insight into their mechanism of action. | |
dc.format.medium | Electronic | |
dc.language | eng | |
dc.publisher | eLife | |
dc.relation.haspart | ARTN e74750 | |
dc.rights | Licence for published version: Creative Commons Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Hedgehog | |
dc.subject | dentate gyrus | |
dc.subject | developmental biology | |
dc.subject | mouse | |
dc.subject | neuroscience | |
dc.subject | plexin | |
dc.subject | semaphorin | |
dc.subject | signal transduction | |
dc.subject | Animals | |
dc.subject | Carrier Proteins | |
dc.subject | Cell Adhesion Molecules | |
dc.subject | GTPase-Activating Proteins | |
dc.subject | Hedgehog Proteins | |
dc.subject | Mice | |
dc.subject | Nerve Tissue Proteins | |
dc.subject | Neuropilins | |
dc.subject | Semaphorins | |
dc.subject | Transcription Factors | |
dc.title | Plexins promote Hedgehog signaling through their cytoplasmic GAP activity | |
dc.type | Article | |
dc.identifier.pmid | 36169302 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/193168/2/Plexins promote Hedgehog signaling through their cytoplasmic GAP activity.pdf | |
dc.identifier.doi | 10.7554/eLife.74750 | |
dc.identifier.doi | https://dx.doi.org/10.7302/22813 | |
dc.identifier.source | eLife | |
dc.description.version | Published version | |
dc.date.updated | 2024-05-21T15:16:50Z | |
dc.identifier.orcid | 0000-0001-5656-5519 | |
dc.identifier.orcid | 0000-0002-1193-0188 | |
dc.identifier.orcid | 0000-0002-7574-7163 | |
dc.identifier.orcid | 0000-0002-2926-3336 | |
dc.identifier.orcid | 0000-0003-2323-8313 | |
dc.description.filedescription | Description of Plexins promote Hedgehog signaling through their cytoplasmic GAP activity.pdf : Published version | |
dc.identifier.volume | 11 | |
dc.identifier.startpage | e74750 | |
dc.identifier.name-orcid | Pinskey, JM; 0000-0001-5656-5519 | |
dc.identifier.name-orcid | Hoard, TM; 0000-0002-1193-0188 | |
dc.identifier.name-orcid | Zhao, XF; 0000-0002-7574-7163 | |
dc.identifier.name-orcid | Franks, NE | |
dc.identifier.name-orcid | Frank, ZC | |
dc.identifier.name-orcid | McMellen, AN | |
dc.identifier.name-orcid | Giger, RJ; 0000-0002-2926-3336 | |
dc.identifier.name-orcid | Allen, BL; 0000-0003-2323-8313 | |
dc.working.doi | 10.7302/22813 | en |
dc.owningcollname | Molecular and Behavioral Neurosciences Institute |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.