Editors' ChoiceNeuroscience

TrkB or Not TrkB?

Sci. Signal.  14 Sep 2010:
Vol. 3, Issue 139, pp. ec280
DOI: 10.1126/scisignal.3139ec280

Death of neurons is an important aspect of development of the nervous system that is regulated through neurotrophin receptors, which, in the absence of ligand, produce signals that cause apoptosis. This process is widespread in the peripheral nervous system but not in the central nervous system (CNS). Nikoletopoulou et al. present evidence that this difference may result from the particular neurotrophin receptor family member that is expressed most abundantly in the CNS. In an in vitro system with differentiating mouse embryonic stem cells and an in vivo system in which embryos were derived from mouse ES cells, expression of the TrkA or TrkC forms of neurotrophin receptors caused the death of neurons that could be rescued by treatment with neurotrophins. The closely related TrkB receptor, which happens to be the one predominantly expressed in the CNS, did not promote such cell death. The cell death mediated by TrkA and TrkC did not require tyrosine kinase activity of the receptors and also appeared not to be mediated by proteolytic fragments of the receptors. Rather, effects of TrkA and TrkC appeared to be in part mediated by proteolytic fragmentation of another neurotrophin receptor, p75. The authors propose that expansion of the Trk receptor family accompanied the evolution of distinct central and peripheral nervous systems during evolution and thus allowed distinct mechanisms to control cell number through apoptosis in the two parts of the nervous system.

V. Nikoletopoulou, H. Lickert, J. M. Frade, C. Rencurel, P. Giallonardo, L. Zhang, M. Bibel, Y.-A. Barde, Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not. Nature 467, 59–63 (2010). [PubMed]

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