ArticleThe Journal of biological chemistry2008
TRP_2, a lipid/trafficking domain that mediates diacylglycerol-induced vesicle fusion.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- A short-term three dimensional culture-based drug sensitivity test is feasible for malignant bone tumors.Human cell · 2023Article
- An inactivating human TRPC6 channel mutation without focal segmental glomerulosclerosis.Cellular and molecular life sciences : CMLS · 2023Article
- An optically controlled probe identifies lipid-gating fenestrations within the TRPC3 channel.Nature chemical biology · 2018Article
- Activation of endothelial transient receptor potential C3 channel is required for small conductance calcium-activated potassium channel activation and sustained endothelial hyperpolarization and vasodilation of cerebral artery.Journal of the American Heart Association · 2014Article
- Integration of transient receptor potential canonical channels with lipids.Acta physiologica (Oxford, England) · 2012Review
- Article
- Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins.Journal of lipid research · 2010Article
- TRPC channel lipid specificity and mechanisms of lipid regulation.Cell calcium · 2009Review
- Phylogenetic Profiles Reveal Structural and Functional Determinants of Lipid-binding.Journal of proteomics & bioinformatics · 2009Article
- Glutamatergic regulation of serine racemase via reversal of PIP2 inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Phylogenetic profiles reveal structural/functional determinants of TRPC3 signal-sensing antennae.Communicative & integrative biology · 2009Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
We recently modeled transient receptor potential (TRP) channels using the Gestalt Domain Detection Algorithm-Basic Local Alignment Tool (GDDA-BLAST), which derives structural, functional, and evolutionary information from primary amino acid sequences using phylogenetic profiles ( Ko, K. D., Hong, Y., Chang, G. S., Bhardwaj, G., van Rossum, D. B., and Patterson, R. L. (2008) Physics Arch. Quant. Methods arXiv: 0806.2394v1 ). Herein we test our functional predictions for the TRP_2 domain of TRPC3; a domain of unknown function that is conserved in all TRPC channels. Our functional models of this domain identify both lipid binding and trafficking activities. In this study, we reveal: (i) a novel structural determinant of ion channel sensitivity to lipids, (ii) a molecular mechanism for the difference between diacylglycerol (DAG)-sensitive and DAG-insensitive TRPC subfamilies, and (iii) evidence that TRPC3 can comprise part of the vesicle fusion machinery. Indeed, the TRPC3 TRP_2 domain mediates channel trafficking to the plasma membrane and binds to plasma membrane lipids. Further, mutations in TRP_2, which alter lipid binding, also disrupt the DAG-mediated fusion of TRPC3-containing vesicles with the plasma membrane without disrupting SNARE interactions. Importantly, these data agree with the known role of DAG in membrane destabilization, which facilitates SNARE-dependent synaptic vesicle fusion ( Villar, A. V., Goni, F. M., and Alonso, A. (2001) FEBS Lett. 494, 117-120 and Goni, F. M., and Alonso, A. (1999) Prog. Lipid Res. 38, 1-48 ). Taken together, functional models generated by GDDA-BLAST provide a computational platform for deriving domain functionality, which can have in vivo and mechanistic relevance.
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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.