Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases

Seidah, Nabil G.; Benjannet, Suzanne; Pareek, Sangeeta; Chrétien, Michel; Murphy, Richard A.

doi:10.1016/0014-5793(95)01520-5

Cited by 323 publications

(236 citation statements)

References 25 publications

(46 reference statements)

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“…S2B). Besides these two convertases, PC1/3 has been reported to process proBDNF in vitro (24). However, in our hands the levels of hippocampal BDNF in WT and PC1/3 KO mice were indistinguishable (Fig.…”

mentioning

confidence: 48%

Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice

Wetsel

Rodriguiz

Guillemot

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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PC7 belongs to the proprotein convertase family, whose members are implicated in the cleavage of secretory precursors. The in vivo function of PC7 is unknown. Herein, we find that the precursor proBDNF is processed into mature BDNF in COS-1 cells coexpressing proBDNF with either PC7 or Furin. Conversely, the processing of proBDNF into BDNF is markedly reduced in the absence of either Furin or PC7 in mouse primary hepatocytes. In vivo we observe that BDNF and PC7 mRNAs are colocalized in mouse hippocampus and amygdala and that mature BDNF protein levels are reduced in these brain areas in PC7 KO mice but not in the hippocampus of PC1/3 KO mice. Various behavioral tests reveal that in PC7 KO mice spatial memory is intact and plasticity of responding is mildly abnormal. Episodic and emotional memories are severely impaired, but both are rescued with the tyrosine receptor kinase B agonist 7,8-dihydroxyflavone. Altogether, these results support an in vivo role for PC7 in the regulation of certain types of cognitive performance, in part via proBDNF processing. Because polymorphic variants of human PC7 are being characterized, it will be important in future studies to determine their effects on additional physiological and behavioral processes.

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mentioning

confidence: 48%

Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice

Wetsel

Rodriguiz

Guillemot

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…2D). Remarkably, inhibitors for tPA and furin, the extracellular and intracellular proteases known to cleave proBDNF in the brain (29,32), did not inhibit the fluorescence increase (Fig. 2D).…”

Section: Activity-dependent Synaptic Competition In Xenopus Nerve-musclementioning

confidence: 91%

Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses

Yang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

153

129

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Formation of specific neuronal connections often involves competition between adjacent axons, leading to stabilization of the active terminal, while retraction of the less active ones. The underlying molecular mechanisms remain unknown. We show that activitydependent conversion of pro-brain-derived neurotrophic factor (proBDNF) to mature (m)BDNF mediates synaptic competition. Stimulation of motoneurons triggers proteolytic conversion of proBDNF to mBDNF at nerve terminals. In Xenopus nerve-muscle cocultures, in which two motoneurons innervate one myocyte, proBDNFp75 NTR signaling promotes retraction of the less active terminal, whereas mBDNF-tyrosine-related kinase B (TrkB) p75NTR (p75 neurotrophin receptor) facilitates stabilization of the active one. Thus, proBDNF and mBDNF may serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, and activity-dependent conversion of proBDNF to mBDNF may regulate synapse elimination. neuromuscular junction | pro-neurotrophin | synapse competition

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“…Neurotrophins, like most biologically active secreted polypeptides, are synthesized as larger precursor proteins (proneurotrophins) that are proteolytically processed to release the mature neurotrophins (Seidah et al, 1996). However, in some systems, substantial amounts of proneurotrophins are secreted.…”

Section: The Neurotrophin Receptors: a Brief Summary Of Signaling Mecmentioning

confidence: 99%

Neurotrophin receptors: Old friends with new partners

Schecterson

Bothwell

2010

Developmental Neurobiology

112

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ABSTRACT:Neurotrophins are important regulators of embryonic development and adult function of most populations of neurons in vertebrate nervous systems. This signaling system regulates many diverse activities, including survival, axon outgrowth, and synaptic plasticity. In mammals, neurotrophin action is mediated by four receptors, p75 NTR , TrkA, TrkB, and TrkC. Although early studies viewed these receptors as solitary agents in the cells outer membrane, recent discoveries reveal that the cell outer membrane is a crowded and highly interactive neighborhood. Neurotrophin receptors partner with a diverse array of membrane proteins, dramatically expanding their functional repertoire. This review will focus on some of the most recent discoveries concerning the promiscuous partnering of neurotrophin receptors. '

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Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases

Cited by 323 publications

References 25 publications

Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice

Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice

Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses

Neurotrophin receptors: Old friends with new partners

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