Cleavage of proBDNF to BDNF by a tolloid-like metalloproteinase is required for acquisition of in vitro eyeblink classical conditioning.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Joyce KeiferTimothy G Clark

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 min...Continue Reading

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Citations

Jun 16, 2010·Journal of Molecular Neuroscience : MN·Boris Sabirzhanov, Joyce Keifer
Mar 26, 2011·Journal of Molecular Neuroscience : MN·Boris SabirzhanovJoyce Keifer
Jun 10, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Wei LiJoyce Keifer
Jul 22, 2010·The European Journal of Neuroscience·J Keifer, Z Zheng
Sep 5, 2015·Epigenetics : Official Journal of the DNA Methylation Society·Ganesh AmbigapathyJoyce Keifer
Dec 9, 2014·Brain Research·Thomas J Nelson, Daniel L Alkon
Jan 18, 2018·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Bin YiHao Wu
Jun 5, 2013·Reviews in the Neurosciences·Hideki TamuraSadao Shiosaka
Jan 29, 2019·Frontiers in Cellular Neuroscience·Claire Emma McGregor, Arthur W English
Oct 8, 2020·Journal of Molecular Neuroscience : MN·Zhaoqing Zheng, Joyce Keifer
Sep 29, 2011·Archives of Medical Research·Haydeé Rosas-VargasThierry Bienvenu

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