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Sci. Signal., 12 February 2013
Vol. 6, Issue 262, p. pe6
[DOI: 10.1126/scisignal.2003824]


Of Proneurotrophins and Their Antineurotrophic Effects

Lucy Kotlyanskaya1,2, Kristina A. McLinden1, and Edward Giniger1*

1 National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20854, USA.
2 Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA.

Abstract: 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.

* Corresponding author. E-mail: ginigere{at}

Citation: L. Kotlyanskaya, K. A. McLinden, E. Giniger, Of Proneurotrophins and Their Antineurotrophic Effects. Sci. Signal. 6, pe6 (2013).

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