Neurotrophin Receptor Death Partner

Abstract

Neurotrophins, such as nerve growth factor (NGF), are most commonly associated with promoting nerve cell survival and differentiation. However, activation of the low-affinity neurotrophin receptor, p75NTR, which has an intracellular, COOH-terminal type-2 death domain, can lead to apoptosis of nerve cells. Mukai et al . have identified the protein NADE (p75NTR-associated cell death executor) in a yeast two-hybrid screen for proteins that interact with the intracellular domain of p75NTR. NADE and p75NTR could be coprecipitated from pheochromocytoma and neuroblastoma cells treated with NGF. When NADE and p75NTR were coexpressed in 293 cells or when NADE alone was transfected into pheochromocytoma cells, NGF-induced activation of caspase-2 and caspase-3 and apoptosis. In oligodendrocytes, a type of glia, NADE expression was induced by treatment of glial cells with NGF and correlated with increased numbers of apoptotic cells. NADE contains a nuclear export sequence and ubiquitination sequences and may represent a regulated component of the cell death pathway mediated by p75NTR. Mukai, J., Hachiya, T., Shoji-Hoshino, S., Kimura, M.T., Nadano, D., Suvanto, P., Hanaoka, T., Li, Y., Irie, S., Greene, L.A., and Sato, T.-A. (2000) NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR. J. Biol. Chem. 275 : 17566-17570. [Abstract] [Full Text]