Extracellular and intracellular cleavages of proBDNF required at two distinct stages of late-phase LTP

NPJ Science of Learning
Petti T PangBai Lu

Abstract

Although late-phase long-term potentiation (L-LTP) is implicated in long-term memory, its molecular mechanisms are largely unknown. Here we provide evidence that L-LTP can be divided into two stages: an induction stage (I) and a maintenance stage (II). Both stages require mature brain-derived neurotrophic factor (mBDNF), but involve distinct underlying mechanisms. Stage I requires secretion of existing proBDNF followed by extracellular cleavage by tPA/plasmin. Stage II depends on newly synthesized BDNF. Surprisingly, mBDNF at stage II is derived from intracellular cleavage of proBDNF by furin/PC1. Moreover, stage I involves BDNF-TrkB signaling mainly through MAP kinase, whereas all three signaling pathways (phospholipase C-γ, PI3 kinase, and MAP kinase) are required for the maintenance of L-LTP at stage II. These results reveal the molecular basis for two temporally distinct stages in L-LTP, and provide insights on how BDNF modulates this long-lasting synaptic alternation at two critical time windows.

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Citations

Dec 16, 2017·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Benjamin HingJames B Potash
May 11, 2016·NPJ Science of Learning·Pankaj SahStephen Williams
May 1, 2021·Biomolecules·Gordana Nedic ErjavecNela Pivac
Jun 12, 2021·Behavioural Brain Research·Geovan Menezes de SousaNicole Leite Galvão-Coelho
Jun 30, 2021·AIMS Neuroscience·Damien Moore, Paul D Loprinzi

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