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© The Rockefeller University Press, 0021-9525/2003/6/1007-b $5.00
The Journal of Cell Biology, Volume 161, Number 6, 1007-b-1007

NRG-1 talks back to neurons

The intracellular domain of Nrg-1 (red) moves to the nucleus (blue) upon erbB treatment (right).

On page 1133, Bao et al. demonstrate that a neuronal growth factor signals to neighboring cells while also communicating back to the nucleus of its own cell. This two-way signaling is necessary to maintain neuronal survival.

In the forward direction, either a soluble or membrane-bound form of the Nrg-1 growth factor activates erbB receptor tyrosine kinases on a variety of adjacent cells. The Nrg-1/erbB partnership is well known to control responses in the erbB-expressing cells, such as epithelial cell motility and proliferation, through MAP kinase pathways. Now, the target cells are shown to talk back to neurons that express membrane-bound Nrg-1 via the same erbB–Nrg-1 complex.Bao et al. show that treatment with soluble erbB protects Nrg-1–expressing neurons from cell death in vitro. The protective activity appears to stem from Nrg-1's ability to regulate transcription of apoptotic genes, including BAK and RIP, whose expression levels were repressed by treatment with erbB. Membrane-bound Nrg-1 was cleaved by a -secretase–like activity in response to erbB treatment, thus releasing the Nrg-1 intracellular domain, which moved to the nucleus. Although Nrg-1 has not been shown to bind to DNA, the authors demonstrate that it does has transactivating activity on a reporter construct, and preliminary evidence indicates it may interact with zinc finger–containing transcription factors.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Back signaling by the Nrg-1 intracellular domain

Jianxin Bao, Deon Wolpowitz, Lorna W. Role, and David A. Talmage
J. Cell Biol. 2003 161: 1133-1141. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 658K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?