ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Cleavage of proBDNF to BDNF by a tolloid-like metalloproteinase is required for acquisition of in vitro eyeblink classical conditioning.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Efficient Production of Recombinant Human Brain-Derived Neurotrophic Factor inInternational journal of molecular sciences · 2024Article
- Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo.Molecular psychiatry · 2024Article
- Review
- Synaptic Mechanisms of Delay Eyeblink Classical Conditioning: AMPAR Trafficking and Gene Regulation in an In Vitro Model.Molecular neurobiology · 2023Review
- Anxiolytic reversal of classically conditioned / chronic stress-induced gene expression and learning in the Stress Alternatives Model.Behavioural brain research · 2023Article
- Comparative Genomics of the BDNF Gene, Non-Canonical Modes of Transcriptional Regulation, and Neurological Disease.Molecular neurobiology · 2021Review
- Learning-Dependent Transcriptional Regulation of BDNF by its Truncated Protein Isoform in Turtle.Journal of molecular neuroscience : MN · 2021Article
- Notoginsenoside R1 Improves Cerebral Ischemia/Reperfusion Injury by Promoting Neurogenesis via the BDNF/Akt/CREB Pathway.Frontiers in pharmacology · 2021Article
- Long-term Administration of Salicylate-induced Changes in BDNF Expression and CREB Phosphorylation in the Auditory Cortex of Rats.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2018Article
- The Role of BDNF in Peripheral Nerve Regeneration: Activity-Dependent Treatments and Val66Met.Frontiers in cellular neuroscience · 2018Review
- Multifaceted Roles of Metzincins in CNS Physiology and Pathology: From Synaptic Plasticity and Cognition to Neurodegenerative Disorders.Frontiers in cellular neuroscience · 2017Review
- Tissue plasminogen activator (tPA) attenuates propofol-induced apoptosis in developing hippocampal neurons.SpringerPlus · 2016Article
- Coincidence detection in a neural correlate of classical conditioning is initiated by bidirectional 3-phosphoinositide-dependent kinase-1 signalling and modulated by adenosine receptors.The Journal of physiology · 2015Article
- Regulation of BDNF chromatin status and promoter accessibility in a neural correlate of associative learning.Epigenetics · 2015Article
- Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder.Biological psychiatry · 2013Article
- ProBDNF and its receptors are upregulated in glioma and inhibit the growth of glioma cells in vitro.Neuro-oncology · 2013Article
- Identification of a functionally distinct truncated BDNF mRNA splice variant and protein in Trachemys scripta elegans.PloS one · 2013Article
- Two-stage AMPA receptor trafficking in classical conditioning and selective role for glutamate receptor subunit 4 (tGluA4) flop splice variant.Journal of neurophysiology · 2012Article
- Rapid enrichment of presynaptic protein in boutons undergoing classical conditioning is mediated by brain-derived neurotrophic factor.Neuroscience · 2012Article
- Exercise influences hippocampal plasticity by modulating brain-derived neurotrophic factor processing.Neuroscience · 2011Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The tolloid/bone morphogenetic protein-1 family of metalloproteinases have an important role in the regulation of embryonic pattern formation and tissue morphogenesis. Studies suggest that they participate in mechanisms of synaptic plasticity in adults, but very little is known about their function. Recently, we isolated a reptilian ortholog of the tolloid gene family designated turtle tolloid-like gene (tTll). Here, we examined the role of tTLL in an in vitro model of eyeblink classical conditioning using an isolated brainstem preparation to assess its role in synaptic plasticity during conditioning. Analysis by real-time reverse transcription-PCR shows that an extracellularly secreted form of tTLL, tTLLs, is transiently expressed in the early stages of conditioning during conditioned response acquisition, whereas a cytosolic form, tTLLc, is not. Short interfering RNA (siRNA)-directed gene knockdown and rescue of tTLL expression demonstrate that it is required for conditioning. Significantly, we show that tTLLs cleaves the precursor proBDNF into mature BDNF in cleavage assay studies, and application of recombinant tTLLs protein alone to preparations results in induction of mature BDNF expression. The mature form of BDNF is minimally expressed in preparations treated with anti-tTLL siRNA, and the synaptic incorporation of both GluR1- and GluR4-containing AMPA receptors is significantly reduced, resulting in suppression of conditioning. This is the first study to demonstrate that expression of an extracellularly secreted tolloid-like metalloproteinase is regulated in the early stages of classical conditioning and functions in the conversion of proBDNF to mature BDNF. The mature form of BDNF is required for synaptic delivery of AMPA receptors and acquisition of conditioned responses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.