ArticleMolecular and cellular neurosciences2012
Protein kinase Cα and integrin-linked kinase mediate the negative axon guidance effects of Sonic hedgehog.
Article in Molecular and cellular neurosciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Calcium dynamics at the neural cell primary cilium regulate Hedgehog signaling-dependent neurogenesis in the embryonic neural tube.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Syntaxin-1 is necessary for UNC5A-C/Netrin-1-dependent macropinocytosis and chemorepulsion.Frontiers in molecular neuroscience · 2023Article
- The Emerging Field of Noncoding RNAs and Their Importance in Pediatric Diseases.The Journal of pediatrics · 2020Article
- Osteoblasts are inherently programmed to repel sensory innervation.Bone research · 2020Article
- Expression and significance of the Hedgehog signal transduction pathway in oxygen-induced retinal neovascularization in mice.Drug design, development and therapy · 2018Article
- Sonic -'Jack-of-All-Trades' in Neural Circuit Formation.Journal of developmental biology · 2017Review
- Contributions of Noncanonical Smoothened Signaling During Embryonic Development.Journal of developmental biology · 2017Article
- Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury.Molecular neurobiology · 2015Article
- Spatiotemporal integration of developmental cues in neural development.Developmental neurobiology · 2015Review
- Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma.Human genetics · 2014Article
- Connecting the retina to the brain.ASN neuro · 2014Review
- Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model.RNA biology · 2013Article
- Sonic hedgehog and Wnt: antagonists in morphogenesis but collaborators in axon guidance.Frontiers in cellular neuroscience · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
In addition to its role as a morphogen, Sonic hedgehog (Shh) has also been shown to function as a guidance factor that directly acts on the growth cones of various types of axons. However, the noncanonical signaling pathways that mediate the guidance effects of Shh protein remain poorly understood. We demonstrate that a novel signaling pathway consisting of protein kinase Cα (PKCα) and integrin-linked kinase (ILK) mediates the negative guidance effects of high concentration of Shh on retinal ganglion cell (RGC) axons. Shh rapidly increased Ca(2+) level and activated PKCα and ILK in the growth cones of RGC axons. By in vitro kinase assay, PKCα was found to directly phosphorylate ILK on threonine-173 and -181. Inhibition of PKCα or expression of a mutant ILK with the PKCα phosphorylation sites mutated (ILK-DM), abolished the Shh-induced macropinocytosis, growth cone collapse and repulsive axon turning. In vivo, expression of a dominant negative PKCα or ILK-DM disrupted RGC axon pathfinding at the optic chiasm but not the projection toward the optic disk, supporting that this signaling pathway plays a specific role in Shh-mediated negative guidance effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.