Activation of neurotrophin signalling with light‑inducible receptor tyrosine kinases. 2022

Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
Anesthesiology Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China.

Optogenetics combined with protein engineering based on natural light‑sensitive dimerizing proteins has evolved as a powerful strategy to study cellular functions. The present study focused on tropomyosin kinase receptors (Trks) that have been engineered to be light‑sensitive. Trk belongs to the superfamily of receptor tyrosine kinases (RTKs), which are single‑pass transmembrane receptors that are activated by natural ligands and serve crucial roles in cellular growth, differentiation, metabolism and motility. However, functional variations exist among receptors fused with light‑sensitive proteins. The present study proposed a signal transduction model for light‑induced receptor activation. This model is based on analysis of previous light‑induced Trk receptors reported to date and comparisons to the activation mechanism of natural receptors. In this model, quantitative differences on the dimerization induced from either top‑to‑bottom or bottom‑to‑up may lead to the varying amplitude of intracellular signals. We hypothesize that the top‑to‑bottom propagation is more favourable for activation and yields better results compared with the bottom‑to‑top direction. The careful delineation of the dimerization mechanisms fine‑tuning activation will guide future design for an optimum cellular output with the precision of light.

UI MeSH Term Description Entries
D008027 Light That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range. Light, Visible,Photoradiation,Radiation, Visible,Visible Radiation,Photoradiations,Radiations, Visible,Visible Light,Visible Radiations
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009414 Nerve Growth Factors Factors which enhance the growth potentialities of sensory and sympathetic nerve cells. Neurite Outgrowth Factor,Neurite Outgrowth Factors,Neuronal Growth-Associated Protein,Neuronotrophic Factor,Neurotrophic Factor,Neurotrophic Factors,Neurotrophin,Neurotrophins,Growth-Associated Proteins, Neuronal,Neuronal Growth-Associated Proteins,Neuronotrophic Factors,Neurotrophic Protein,Neurotrophic Proteins,Proteins, Neuronal Growth-Associated,Factor, Neurite Outgrowth,Factor, Neuronotrophic,Factor, Neurotrophic,Factors, Nerve Growth,Factors, Neurite Outgrowth,Factors, Neuronotrophic,Factors, Neurotrophic,Growth Associated Proteins, Neuronal,Growth-Associated Protein, Neuronal,Neuronal Growth Associated Protein,Neuronal Growth Associated Proteins,Outgrowth Factor, Neurite,Outgrowth Factors, Neurite,Protein, Neuronal Growth-Associated
D011972 Receptor, Insulin A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE. Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D055537 Light Signal Transduction The conversion of absorbed light energy into molecular signals. Phototransduction,Signal Transduction, Light,Transduction, Light Signal
D019281 Dimerization The process by which two molecules of the same chemical composition form a condensation product or polymer. Dimerizations
D020794 Receptor Protein-Tyrosine Kinases A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity. PTK Receptor,Receptors, Protein-Tyrosine Kinase,Tyrosine Kinase Linked Receptor,Tyrosine Kinase Linked Receptors,Tyrosine Kinase Receptor,Tyrosine Kinase Receptors,PTK Receptors,Protein-Tyrosine Kinase Receptor,Receptor Protein-Tyrosine Kinase,Kinase Receptor, Tyrosine,Kinase, Receptor Protein-Tyrosine,Kinases, Receptor Protein-Tyrosine,Protein-Tyrosine Kinase Receptors,Protein-Tyrosine Kinase, Receptor,Protein-Tyrosine Kinases, Receptor,Receptor Protein Tyrosine Kinase,Receptor Protein Tyrosine Kinases,Receptor, PTK,Receptor, Protein-Tyrosine Kinase,Receptor, Tyrosine Kinase,Receptors, PTK,Receptors, Protein Tyrosine Kinase
D020917 Receptor, trkA A protein-tyrosine kinase receptor that is specific for NERVE GROWTH FACTOR; NEUROTROPHIN 3; neurotrophin 4, neurotrophin 5. It plays a crucial role in pain sensation and thermoregulation in humans. Gene mutations that cause loss of receptor function are associated with CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS, while gene rearrangements that activate the protein-tyrosine kinase function are associated with tumorigenesis. NTRK1 Receptor,Proto-Oncogene Protein trk,Receptor, Neurotrophic Tyrosine Kinase Type 1,gp140(c-TRK),trk Proto-Oncogene Protein,trkA Receptor,Neurotrophic Tyrosine Kinase Receptor Type 1,Proto-Oncogene Products c-trk,c-trk Protein,gp140 c-trk,p140-trkA,trk1 Transforming Tryrosine Kinase,Proto Oncogene Products c trk,Proto Oncogene Protein trk,Proto-Oncogene Protein, trk,Receptor, NTRK1,c trk Protein,c-trk, Proto-Oncogene Products,c-trk, gp140,gp140 c trk,p140 trkA,trk Proto Oncogene Protein,trk, Proto-Oncogene Protein

Related Publications

Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
June 2014, Nature communications,
Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
March 2019, Nature communications,
Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
October 2003, Journal of neuroscience research,
Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
January 1993, Annual review of biochemistry,
Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
August 2014, The EMBO journal,
Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
March 1993, BioEssays : news and reviews in molecular, cellular and developmental biology,
Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
January 2000, Breast cancer research : BCR,
Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
December 1994, Journal of the American Society of Nephrology : JASN,
Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
July 1994, Circulation research,
Wei Zhang, and Shu Zhao, and Linjie Lu, and Zhimin Fan, and Shixin Ye
August 2006, Biochemical Society transactions,
Copied contents to your clipboard!