Abstract
Brain-derived neurotrophic factor (BDNF) is critical for mammalian development and plasticity of neuronal circuitries affecting memory, mood, anxiety, pain sensitivity, and energy homeostasis. Here we report a novel unexpected role of BDNF in regulating the cardiac contraction force independent of the nervous system innervation. This function is mediated by the truncated TrkB.T1 receptor expressed in cardiomyocytes. Loss of TrkB.T1 in these cells impairs calcium signaling and causes cardiomyopathy. TrkB.T1 is activated by BDNF produced by cardiomyocytes, suggesting an autocrine/paracrine loop. These findings unveil a novel signaling mechanism in the heart that is activated by BDNF and provide evidence for a global role of this neurotrophin in the homeostasis of the organism by signaling through different TrkB receptor isoforms.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Autocrine Communication
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Brain-Derived Neurotrophic Factor / genetics
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Brain-Derived Neurotrophic Factor / metabolism*
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Brain-Derived Neurotrophic Factor / pharmacology
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Calcium Signaling
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Cardiomyopathies / enzymology*
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Cardiomyopathies / genetics
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Cardiomyopathies / pathology
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Cardiomyopathies / physiopathology
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Enzyme Activation
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Genotype
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Isolated Heart Preparation
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Male
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Mice, Knockout
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Mice, Transgenic
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Muscle Strength* / drug effects
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Myocardial Contraction* / drug effects
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Myocytes, Cardiac / drug effects
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Myocytes, Cardiac / enzymology*
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Myocytes, Cardiac / pathology
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Paracrine Communication
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Phenotype
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Protein-Tyrosine Kinases / deficiency
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Signal Transduction
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Time Factors
Substances
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Brain-Derived Neurotrophic Factor
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Membrane Glycoproteins
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Ntrk2 protein, mouse
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Protein-Tyrosine Kinases