BDNF modulates heart contraction force and  long-term homeostasis through truncated TrkB.T1  receptor activation.
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.
Gianluca
G
Fulgenzi
Francesco
F
Tomassoni-Ardori
Lucia
L
Babini
Jodi
J
Becker
Colleen
C
Barrick
Sandrine
S
Puverel
Lino
L
Tessarollo
D000818:Animals; D019898:Autocrine Communication; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling; D009202:Cardiomyopathies / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004789:Enzyme Activation; D005838:Genotype; D000067268:Isolated Heart Preparation; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053580:Muscle Strength / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D019899:Paracrine Communication; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D020813:Receptor, trkB
D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; C064371:Ntrk2 protein, mouse; D020813:Receptor, trkB