PMID- 28572757
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220331
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 10
DP  - 2017
TI  - Muscle Contraction Regulates BDNF/TrkB Signaling to Modulate Synaptic Function 
      through Presynaptic cPKCalpha and cPKCbetaI.
PG  - 147
LID - 10.3389/fnmol.2017.00147 [doi]
LID - 147
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) acts via 
      tropomyosin-related kinase B receptor (TrkB) to regulate synapse maintenance and 
      function in the neuromuscular system. The potentiation of acetylcholine (ACh) 
      release by BDNF requires TrkB phosphorylation and Protein Kinase C (PKC) 
      activation. BDNF is secreted in an activity-dependent manner but it is not known 
      if pre- and/or postsynaptic activities enhance BDNF expression in vivo at the 
      neuromuscular junction (NMJ). Here, we investigated whether nerve and muscle cell 
      activities regulate presynaptic conventional PKC (cPKCalpha and betaI) via BDNF/TrkB 
      signaling to modulate synaptic strength at the NMJ. To differentiate the effects 
      of presynaptic activity from that of muscle contraction, we stimulated the 
      phrenic nerve of rat diaphragms (1 Hz, 30 min) with or without contraction 
      (abolished by mu-conotoxin GIIIB). Then, we performed ELISA, Western blotting, 
      qRT-PCR, immunofluorescence and electrophysiological techniques. We found that 
      nerve-induced muscle contraction: (1) increases the levels of mature BDNF protein 
      without affecting pro-BDNF protein or BDNF mRNA levels; (2) downregulates TrkB.T1 
      without affecting TrkB.FL or p75 neurotrophin receptor (p75) levels; (3) 
      increases presynaptic cPKCalpha and cPKCbetaI protein level through TrkB signaling; and 
      (4) enhances phosphorylation of cPKCalpha and cPKCbetaI. Furthermore, we demonstrate 
      that cPKCbetaI, which is exclusively located in the motor nerve terminals, increases 
      activity-induced acetylcholine release. Together, these results show that 
      nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling 
      pathway, retrogradely activating presynaptic cPKC isoforms (in particular cPKCbetaI) 
      to modulate synaptic function. These results indicate that a decrease in 
      neuromuscular activity, as occurs in several neuromuscular disorders, could 
      affect the BDNF/TrkB/PKC pathway that links pre- and postsynaptic activity to 
      maintain neuromuscular function.
FAU - Hurtado, Erica
AU  - Hurtado E
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
FAU - Cilleros, Victor
AU  - Cilleros V
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
FAU - Nadal, Laura
AU  - Nadal L
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
FAU - Simo, Anna
AU  - Simo A
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
FAU - Obis, Teresa
AU  - Obis T
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
FAU - Garcia, Neus
AU  - Garcia N
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
FAU - Santafe, Manel M
AU  - Santafe MM
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
FAU - Tomas, Marta
AU  - Tomas M
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
FAU - Halievski, Katherine
AU  - Halievski K
AD  - Neuroscience Program, Michigan State UniversityMichigan, MI, United States.
FAU - Jordan, Cynthia L
AU  - Jordan CL
AD  - Neuroscience Program, Michigan State UniversityMichigan, MI, United States.
FAU - Lanuza, Maria A
AU  - Lanuza MA
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
FAU - Tomas, Josep
AU  - Tomas J
AD  - Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciencies 
      de la Salut, Universitat Rovira i VirgiliReus, Spain.
LA  - eng
GR  - R01 NS045195/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20170518
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5436293
OTO - NOTNLM
OT  - Bdnf-TrkB signaling
OT  - PKC
OT  - muscle contraction
OT  - neuromuscular junction
OT  - neurotransmission
EDAT- 2017/06/03 06:00
MHDA- 2017/06/03 06:01
PMCR- 2017/01/01
CRDT- 2017/06/03 06:00
PHST- 2017/03/20 00:00 [received]
PHST- 2017/05/01 00:00 [accepted]
PHST- 2017/06/03 06:00 [entrez]
PHST- 2017/06/03 06:00 [pubmed]
PHST- 2017/06/03 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2017.00147 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2017 May 18;10:147. doi: 10.3389/fnmol.2017.00147. 
      eCollection 2017.