ProBDNF and Mature BDNF as Punishment and Reward Signals for Synapse Elimination at Mouse Neuromuscular Junctions

@article{Je2013ProBDNFAM,
  title={ProBDNF and Mature BDNF as Punishment and Reward Signals for Synapse Elimination at Mouse Neuromuscular Junctions},
  author={H Shawn Je and Feng Yang and Yuanyuan Ji and Srilatha Potluri and Xiu-Qing Fu and Zhen-Ge Luo and Guhan Nagappan and Jia Pei Chan and Barbara L. Hempstead and Young-Jin Son and Bai Lu},
  journal={The Journal of Neuroscience},
  year={2013},
  volume={33},
  pages={9957 - 9962}
}
During development, mammalian neuromuscular junctions (NMJs) transit from multiple-innervation to single-innervation through axonal competition via unknown molecular mechanisms. Previously, using an in vitro model system, we demonstrated that the postsynaptic secretion of pro-brain-derived neurotrophic factor (proBDNF) stabilizes or eliminates presynaptic axon terminals, depending on its proteolytic conversion at synapses. Here, using developing mouse NMJs, we obtained in vivo evidence that… 

Figures from this paper

Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum
TLDR
The authors show that BDNF-TrkB retrograde signaling is a “punishment” signal that leads to elimination of climbing fiber-onto-Purkinje cell synapses in the developing cerebellum.
Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development
TLDR
A molecular background for developmental axonal competition and loss is proposed and transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors, adenosine autoreception and trophic factor receptors are studied during the development of NMJ and in the adult.
The p75NTR neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availability
TLDR
Results on primary myotubes and denervated muscles indicate that muscle-derived p75NTR does not play a major role on postsynaptic organization, and reveal that pharmacological acetylcholinesterase inhibition rescued nerve-dependent muscle response and force production in p 75NTR null mice.
Muscle Contraction Regulates BDNF/TrkB Signaling to Modulate Synaptic Function through Presynaptic cPKCα and cPKCβI
TLDR
Results show that nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling pathway, retrogradely activating presynaptic cPKC isoforms (in particular cP KCβI) to modulate synaptic function, and indicates that a decrease in neuromuscular activity could affect the BDNF-TrkB/PKC pathway that links pre- and postsynaptic activity to maintain neuromUScular function.
The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling
TLDR
Synaptic activity modulation of the BDNF/TrkB/PKC signaling to sustain NMJ function, its and other kinases’ disturbances in ALS and physical and molecular mechanisms to delay disease progression are reviewed.
Pro-Brain-Derived Neurotrophic Factor Inhibits GABAergic Neurotransmission by Activating Endocytosis and Repression of GABAA Receptors
TLDR
It is demonstrated that proBDNF impairs GABAergic transmission by the activation of two distinct pathways: a RhoA-Rock-PTEN pathway that decreases the phosphorylation levels of GABAAR, thus affecting receptor function and triggering endocytosis and degradation of internalized receptors, and a JAK-STAT-ICER pathway leading to the repression ofGAARs synthesis.
ProBDNF and Brain-Derived Neurotrophic Factor Prodomain Differently Modulate Acetylcholine Release in Regenerating and Mature Mouse Motor Synapses
TLDR
The data obtained suggest that there is a previously unknown mechanism for the acute suppression of spontaneous and evoked ACh release in mature motor synapses, which involves the activation of p75 receptors, ROCK and GIRK channels by BDNF prodomain and requires interaction with metabotropic purinoreceptors.
Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity
TLDR
A RA-mediated retrograde synaptic signaling pathway through which postsynaptic protein synthesis during synaptic inactivity drives compensatory changes at presynaptic site is illustrated.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 35 REFERENCES
Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses
TLDR
ProBDNF and mBDNF may serve as potential “punishment” and “reward” signals for inactive and active terminals, respectively, and activity-dependent conversion of proBDNF to mBD NF may regulate synapse elimination.
Pro-BDNF–induced synaptic depression and retraction at developing neuromuscular synapses
TLDR
Evidence is provided that pro–brain-derived neurotrophic factor is a negative retrograde signal that can be converted into a positive signal by metalloproteases at the synaptic junctions, and a model in which postsynaptic secretion of a single molecule, pro-BDNF, may stabilize or eliminate presynaptic terminals depending on its proteolytic conversion at the synapses.
Activity-dependent elimination of neuromuscular synapses
TLDR
Current ideas about how activity modulates neuromuscular synaptic competition, how competition leads to synapse loss, and how these processes are modulated by cell-cell signaling are discussed.
Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury
TLDR
The sortilin pathway has distinct roles in pro-neurotrophin–induced apoptotic signaling in pathological conditions, but also in specific stages of neuronal development and aging.
ProBDNF Induces Neuronal Apoptosis via Activation of a Receptor Complex of p75NTR and Sortilin
TLDR
In sympathetic neurons coexpressing sortilin and p75NTR, it is found that proBDNF is an apoptotic ligand that induces death at subnanomolar concentrations, suggesting that the neurotrophin family is capable of modulating diverse biological processes via differential processing of the proneurotrophins.
Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse
TLDR
It is reported that the initial steps in postsynaptic differentiation and formation of an end-plate band require MuSK and rapsyn, but are not dependent on agrin or the presence of motor axons, while the subsequent stages of synaptic growth and maintenance require nerve-derived agrin, and a second nerve- derived signal that disperses ectopic post synaptic apparatus.
Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4
TLDR
The results suggest that another ligand, perhaps NT3, does indeed act on TrkB in vivo, and that distinct neuronal populations with different neurotrophin requirements require both BDNF and NT4.
Blocking p75NTR receptors alters polyinnervationz of neuromuscular synapses during development
TLDR
The results indicate that p75NTR is involved in both ACh release and axonal retraction during postnatal axonal competition and synapse elimination in postnatal rats.
...
1
2
3
4
...