SCIENCE SIGNALING

A Receptor for Neurotrophins

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Science  29 Feb 2008:
Vol. 319, Issue 5867, pp. 1163
DOI: 10.1126/science.319.5867.1163c

Integrins are dimeric cell surface receptors composed αof and β subunits and interact with the extracellular matrix (ECM) to promote cell adhesion and survival. There are 18 α and 8 β subunits in mammals, and at least 24 heterodimers have been described. Given this complexity, it is not surprising that integrins have been observed to interact with molecules other than those in the ECM. For example, α9β1, a widely distributed integrin, interacts with several classes of ligands, including ECM constituents (tenascin, thrombospondin 1, and osteopontin), metalloproteases (ADAM12 and 15), and vascular endothelial growth factor. Staniszewska et al. report that integrin α9β1 also binds to the neurotrophins NGF, NT3, and BDNF. They found that an α9β1-transfected colon cancer cell line adhered to mouse NGF, human recombinant NGF, BDNF, or NT3 with the same efficiency as to VCAM1, a known α9β1 ligand. Adherence was blocked by an α9β1-specific antibody and by a snake venom protein that selectively antagonizes α9β1. Human recombinant NGF bound to α9β1 with a Kd of about 5 nM, which is similar to the strength of the interaction between NGF and the low-affinity receptor p75NTR. The responses of the transfected cells to NGF included proliferation (involving extracellular signal-regulated kinases 1 and 2) and migration (involving paxillin). — NRG

J. Cell Sci. 121, 504 (2008).

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