Cell Signaling

ProNGF is Anti Growth

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Science  16 Dec 2011:
Vol. 334, Issue 6062, pp. 1473
DOI: 10.1126/science.334.6062.1473-a

Nerve growth factor (NGF) can influence multiple activities of neurons including survival, differentiation, and migration. The broad array of effects results in part from interaction with multiple distinct receptors and receptor complexes. Adding further to the regulatory versatility, NGF peptides are made in a precursor form (proNGF) that is proteolytically processed to form mature NGF, and this proNGF form has distinct biological effects. In cultured rat or mouse hippocampal neurons, Deinhardt et al. show that although NGF promotes neurite extension, proNGF caused growth cone collapse. ProNGF acted through the p75 neurotrophin receptor complexed with the sortilin family member SorCS2. This caused inhibition of the small guanosine triphosphatase Rac and inactivation of the actin-binding protein fascin, thus leading to collapse of growth cones. Because proNGF and the p75 neurotrophin receptor accumulate after nerve injury, they may contribute to impaired neuronal recovery after injury or in neurodegenerative diseases.

Sci. Sig. 4, ra82 (2011).

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