A Signaling Endosome Hypothesis to Explain NGF Actions: Potential Implications for Neurodegeneration
- 1Department of Physiology, 2Department of Neurology, and 3The Neuroscience Program, University of California, San Francisco, California 94143; 4Department of Biochemistry, Massey University, Palmerston North, New Zealand
- 5
↵5 These authors contributed equally to the work.
This extract was created in the absence of an abstract.
Excerpt
Nerve growth factor (NGF), a polypeptide neurotrophic factor of the neurotrophin (NT) gene family, acts to enhance the survival and differentiation of specific populations of neurons in the central (CNS) and peripheral (PNS) nervous systems (Levi-Montalcini 1987; Yuen and Mobley 1995). NGF acts by binding to both high- and low-affinity receptors. Its receptors are p75NGFR and TrkA. p75NGFR is a receptor for all the neurotrophins, exhibiting binding affinities in the nanomolar range (i.e., low-affinity binding) (Meakin and Shooter 1992; Bothwell 1995). The role that p75NGFR plays in NGF signaling is not well defined; however, in addition to a direct signaling function (Bothwell 1996; Carter et al. 1996; Taglialatela et al. 1996), p75NGFR has been shown to modulate NGF binding and activation of TrkA (Meakin and Shooter 1992; Davies et al. 1993; Barker and Shooter 1994; Hantzopoulos et al. 1994; Mahadeo et al. 1994; Verdi et al. 1994; Bothwell 1995). TrkA...
