Of Proneurotrophins and Their Antineurotrophic Effects

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Science Signaling  12 Feb 2013:
Vol. 6, Issue 262, pp. pe6
DOI: 10.1126/scisignal.2003824

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Neurotrophins perform essential processes throughout neural development. They signal through Trk receptor proteins, typically in association with a “low affinity” p75NTR pan-neurotrophin co-receptor. Neurotrophins are synthesized as proproteins; the pro domains are removed proteolytically to yield the mature, presumably functional forms of the neurotrophins. Recent findings, however, have revealed a positive role for the proneurotrophins themselves. The proproteins bind with high affinity to the p75NTR pan-neurotrophin receptor in the absence of Trks to initiate a separate set of signaling cascades that actively oppose the effects of the mature growth factors. These experiments suggest that the balance between pro- and mature neurotrophin plays a critical role in tuning downstream signaling. This view changes the neurotrophin field substantially and also points to the broader idea that the potential activities of precursor proteins deserve a closer look.

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