Last update 21 Mar 2024
TREK2
potassium two pore domain channel subfamily K member 10
Last update 21 Mar 2024
Basic Info
Synonyms K2p10.1, KCNK10, Outward rectifying potassium channel protein TREK-2 + [9] |
Introduction Outward rectifying potassium channel. Produces rapidly activating and non-inactivating outward rectifier K(+) currents. Activated by arachidonic acid and other naturally occurring unsaturated free fatty acids. |
Related
100 Clinical Results associated with TREK2
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100 Translational Medicine associated with TREK2
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0 Patents (Medical) associated with TREK2
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219
Literatures (Medical) associated with TREK201 Dec 2023·Journal of the Endocrine Society
Differential Effects of PTH (1-34), PTHrP (1-36), and Abaloparatide on the Murine Osteoblast Transcriptome.
Article
Author: Michael J Mosca ; Zhiming He ; Florante R Ricarte ; Carole Le Henaff ; Nicola C Partridge
Teriparatide (PTH (1-34)), PTHrP (1-36), and abaloparatide (ABL) have been used for the treatment of osteoporosis, but their efficacy long term is significantly limited. The 3 peptides exert time- and dose-dependent differential responses in osteoblasts, leading us to hypothesize they may also differentially modulate the osteoblast transcriptome. Treatment of mouse calvarial osteoblasts with 1 nM of the peptides for 4 hours results in RNA sequencing data with PTH (1-34) regulating 367 genes, including 194 unique genes; PTHrP (1-36) regulating 117 genes, including 15 unique genes; and ABL regulating 179 genes, including 20 unique genes. There were 83 genes shared among all 3 peptides. Gene ontology analyses showed similarities in Wnt signaling, cAMP-mediated signaling, ossification, but differences in morphogenesis of a branching structure in biological processes; receptor ligand activity, transcription factor activity, and cytokine receptor/binding activity in molecular functions. The peptides increased Vdr, Cited1, and Pde10a messenger RNAs (mRNAs) in a pattern similar to Rankl, that is, PTH (1-34) greater than ABL greater than PTHrP (1-36). mRNA abundance of other genes, including Wnt4, Wnt7, Wnt11, Sfrp4, Dkk1, Kcnk10, Hdac4, Epn3, Tcf7, Crem, Fzd5, Ppp2r2a, and Dvl3, showed that some genes were regulated similarly by all 3 peptides; others were not. Finally, small interfering RNA knockdowns of SIK1/2/3 and CRTC1/2/3 in PTH (1-34)-treated cells revealed that Vdr and Wnt4 genes are regulated by salt-inducible kinases (SIKs) and CREB-regulated transcriptional coactivators (CRTCs), while others are not. Although many studies have examined PTH signaling in the osteoblast/osteocyte, ours is the first to compare the global effects of these peptides on the osteoblast transcriptome or to analyze the roles of the SIKs and CRTCs.
16 Aug 2023·bioRxiv : the preprint server for biology
Differential effects of PTH (1-34), PTHrP (1-36) and abaloparatide on the murine osteoblast transcriptome.
Author: Michael J Mosca ; Zhiming He ; Florante R Ricarte ; Carole Le Henaff ; Nicola C Partridge
Teriparatide (PTH(1-34)) and its analogs, PTHrP(1-36) and abaloparatide (ABL) have been used for the treatment of osteoporosis, but their efficacy over long-term use is significantly limited. The 3 peptides exert time- and dose-dependent differential responses in osteoblasts, leading us to hypothesize that they may also differentially modulate the osteoblast transcriptome. We show that treatment of mouse calvarial osteoblasts with 1 nM of the 3 peptides for 4 h results in RNA-Seq data with PTH(1-34) regulating 367 genes, including 194 unique genes; PTHrP(1-36) regulating 117 genes, including 15 unique genes; and ABL regulating 179 genes, including 20 unique genes. There were 83 genes shared among all 3 peptides. Gene ontology analyses showed differences in Wnt signaling, cAMP-mediated signaling, bone mineralization, morphogenesis of a branching structure in biological processes; receptor ligand activity, transcription factor activity, cytokine receptor/binding activity and many other actions in molecular functions. The 3 peptides increased Vdr, Cited1 and Pde10a mRNAs in a pattern similar to Rankl , i.e., PTH(1-34) > ABL > PTHrP(1-36). mRNA abundance of other genes based on gene/pathway analyses, including Wnt4, Wnt7, Wnt11, Sfrp4, Dkk1, Kcnk10, Hdac4, Epha3, Tcf7, Crem, Fzd5, Pp2r2a , and Dvl3 showed that some genes were regulated similarly by all 3 peptides; others were not. Finally, siRNA knockdowns of SIK1/2/3 and CRTC1/2/3 in PTH(1-34)-treated cells revealed that Vdr and Wnt4 genes are regulated by SIKs and CRTCs, while others are not. Although many studies have examined PTH signaling in the osteoblast/osteocyte, ours is the first to examine the global effects of these peptides on the osteoblast transcriptome. Further delineation of which signaling events are attributable to PTH(1-34), PTHrP(1-36) or ABL exclusively and which are shared among all 3 will help improve our understanding of the effects these peptides have on the osteoblast and lead to the refinement of PTH-derived treatments for osteoporosis.
16 Aug 2023·Chemical science
Combining native mass spectrometry and lipidomics to uncover specific membrane protein-lipid interactions from natural lipid sources
Article
Author: Zhu, Yun ; Odenkirk, Melanie T. ; Qiao, Pei ; Zhang, Tianqi ; Schrecke, Samantha ; Zhou, Ming ; Marty, Michael T. ; Baker, Erin S. ; Laganowsky, Arthur
While it is known that lipids play an essential role in regulating membrane protein structure and function, it remains challenging to identify specific protein-lipid interactions. Here, we present an innovative approach that combines native mass spectrometry (MS) and lipidomics to identify lipids retained by membrane proteins from natural lipid extracts. Our results reveal that the bacterial ammonia channel (AmtB) enriches specific cardiolipin (CDL) and phosphatidylethanolamine (PE) from natural headgroup extracts. When the two extracts are mixed, AmtB retains more species, wherein selectivity is tuned to bias headgroup selection. Using a series of natural headgroup extracts, we show TRAAK, a two-pore domain K+ channel (K2P), retains specific acyl chains that is independent of the headgroup. A brain polar lipid extract was then combined with the K2Ps, TRAAK and TREK2, to understand lipid specificity. More than a hundred lipids demonstrated affinity for each protein, and both channels were found to retain specific fatty acids and lysophospholipids known to stimulate channel activity, even after several column washes. Natural lipid extracts provide the unique opportunity to not only present natural lipid diversity to purified membrane proteins but also identify lipids that may be important for membrane protein structure and function.
1
News (Medical) associated with TREK227 Feb 2024
BOSTON, Feb. 27, 2024 (GLOBE NEWSWIRE) -- Cerevance, a company focused on developing precision novel therapeutics for central nervous system (CNS) diseases, today announced plans to present a virtual and onsite poster at the upcoming AD/PD™ 2024 International Conference on Alzheimer's and Parkinson's Diseases and related neurological disorders, taking place in Lisbon, Portugal from March 5-9, 2024.
Presentation details
Title: NETSseq reveals deep molecular insights into astrocyte biology and identifies novel therapeutic targets for Alzheimer’s disease
Overview: The NETSseq platform produces deep transcriptomic and epigenomic profiles from post-mortem human brain tissue. This technology has revealed novel understandings of astrocyte-specific mechanisms influencing disease progression, including a network of genes involved in glutamate signaling that are down-regulated in diseased and activated astrocytes. One of these genes, KCNK10, is specifically expressed in astrocytes and oligodendrocytes, and its role in regulating glutamate uptake has been validated. Modulating KCNK10 activity might mitigate neuronal hyperexcitability and neurodegeneration associated with Alzheimer’s disease.
Presenters: Xiao Xu
Session and Date and Time: A02.N. Therapeutic Targets, Mechanisms for Treatment: Astroglia; Poster Shift 2: Friday, March 8 - Saturday, March 9, 2024
Poster Number: 0126
About Cerevance
Cerevance is focused on the development of precision treatments for central nervous system (CNS) disorders, prioritizing chronic neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis (ALS). Utilizing a large and growing collection of over 14,000 human brain tissue samples, Cerevance is generating an unprecedented level of expression and epigenetic data thereby enabling the company to identify the most promising targets for the next generation of treatments for CNS disorders.
The company uses its proprietary NETSseq platform and advanced machine learning techniques to uncover the gene expression profiles of select cell types to identify novel targets that are uniquely expressed in relevant circuits affected by diseases or are altered in disease states. With the information obtained from its research, combined with the expertise of its team of scientists and drug developers, Cerevance is advancing multiple therapeutics that selectively modulate the discovered targets. These treatments are progressing through clinical development, with CVN424, CVN766, and CVN293 being the furthest along in the pipeline. CVN424 is a first-in-class non-dopamine therapy that shows promise in improving both motor and non-motor symptoms of Parkinson's disease and may also have disease-delaying effects. CVN766 is a potent antagonist of the orexin 1 receptor with high selectivity over the orexin 2 receptor which may benefit a variety of psychiatric conditions including schizophrenia, anxiety/panic, binge eating/obesity, substance use disorder, and Prader-Willi Syndrome. CVN293 is a novel blocker of potassium efflux in glia, regulating the inflammasome in individuals living with ALS and Alzheimer's disease.
Cerevance’s robust pipeline aims to transform the lives of patients affected by CNS diseases.
Contacts
Cerevance:
Johnna Simoes, ir@cerevance.com
Media:
Andrew Mielach, amielach@lifescicomms.com, +1-646-876-5868
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