ArticleProceedings of the National Academy of Sciences of the United States of America2012
Calpain cleaves and activates the TRPC5 channel to participate in semaphorin 3A-induced neuronal growth cone collapse.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- Clemizole, a TRPC5 channel blocker rescues amyloid-β toxicity and cognitive impairment by modulating mitochondrial dysfunction and memory-related proteins.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Calpain cleaves the distal carboxyl terminus of TRPV1 and modulates its tachyphylaxis.Cell & bioscience · 2026Article
- TRPC1 links calcium signaling to cellular senescence in the protection against posttraumatic osteoarthritis.JCI insight · 2024Article
- Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1.Signal transduction and targeted therapy · 2024Article
- Adriamycin-induced podocyte injury via the Sema3A/TRPC5/Rac1 pathway.Frontiers in medicine · 2024Article
- Membrane-anchored calpains - hidden regulators of growth and development beyond plants?Frontiers in plant science · 2023Article
- The key role of Calpain in COVID-19 as a therapeutic strategy.Inflammopharmacology · 2022Review
- The ryanodine receptor mutational characteristics and its indication for cancer prognosis.Scientific reports · 2022Article
- Article
- Role of Oxidative Stress and CaFrontiers in cell and developmental biology · 2021Review
- The Role of TRP Channels and PMCA in Brain Disorders: Intracellular Calcium and pH Homeostasis.Frontiers in cell and developmental biology · 2021Review
- Review
- TRP Channels Regulation of Rho GTPases in Brain Context and Diseases.Frontiers in cell and developmental biology · 2020Review
- TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases.Frontiers in physiology · 2020Review
- Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling.Comprehensive Physiology · 2019Review
- Differential regulation of ion channels function by proteolysis.Biochimica et biophysica acta. Molecular cell research · 2018Review
- TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation.Molecular metabolism · 2018Article
- The calcium-cancer signalling nexus.Nature reviews. Cancer · 2017Review
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- Mitochondrial dynamics in neuronal injury, development and plasticity.Journal of cell science · 2017Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The nonselective cation channel transient receptor potential canonical (TRPC)5 is found predominantly in the brain and has been proposed to regulate neuronal processes and growth cones. Here, we demonstrate that semaphorin 3A-mediated growth cone collapse is reduced in hippocampal neurons from TRPC5 null mice. This reduction is reproduced by inhibition of the calcium-sensitive protease calpain in wild-type neurons but not in TRPC5(-/-) neurons. We show that calpain-1 and calpain-2 cleave and functionally activate TRPC5. Mutation of a critical threonine at position 857 inhibits calpain-2 cleavage of the channel. Finally, we show that the truncated TRPC5 predicted to result from calpain cleavage is functionally active. These results indicate that semaphorin 3A initiates growth cone collapse via activation of calpain that in turn potentiates TRPC5 activity. Thus, TRPC5 acts downstream of semaphorin signaling to cause changes in neuronal growth cone morphology and nervous system development.
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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.