The p75 neurotrophin receptor (p75(NTR)) is involved in numerous neuronal signaling paths but its fundamental signaling mechanisms are unknown. In this issue of Neuron, Vilar et al. show that p75NTR functions as a covalently crosslinked dimer to transduce NGF-induced signaling events.

Prevention by nerve growth factor (NGF) of apoptotic death in neural cells has been variously ascribed to binding of NGF to its low-affinity (p75) or high-affinity (trkA) receptor or to a cooperative interaction between the two. In a series of studies using, in turn, neuroblastoma cell lines that express only p75, mutant NGF species that bind selectively to either p75 or trkA, and a polyclonal ...

The genus Oxystele, a member of the highly diverse marine gastropod superfamily Trochoidea, is endemic to southern Africa. Members of the genus include some of the most abundant molluscs on southern African shores and are important components of littoral biodiversity in rocky intertidal habitats. Species delimitation within the genus is still controversial, especially regarding the complex O. i...

Functional interactions between the p75 neurotrophin receptor (p75NTR) and the Trk receptors were demonstrated several years ago, but their mechanistic basis remains uncertain. In this issue of Neuron, Wehrman et al. provide a three-dimensional structure of the full TrkA ectodomain complexed to NGF and examine the possibility of a ternary p75NTR-NGF-TrkA complex.

The bladder is lined by urothelium a mitoticallyquiescent epithelium in situ characterised by an extremely low turnover rate and long-lived cells. However, in response to injury, infection or other stimuli, the urothelium develops a highly regenerative response. As a self-renewing tissue, there is assumed to be a resident progenitor population. However, no specific population has yet been ident...

The invasive nature of cancers in general, and malignant gliomas in particular, is a major clinical problem rendering tumors incurable by conventional therapies. Using a novel invasive glioma mouse model established by serial in vivo selection, we identified the p75 neurotrophin receptor (p75(NTR)) as a critical regulator of glioma invasion. Through a series of functional, biochemical, and clin...

Duplication of the gene for the peripheral myelin protein 22 (PMP22) is the most common cause for Charcot-Marie-Tooth neuropathy type 1a (CMT1A) neuropathy. In early stages of the disease PMP22 is overexpressed in nerve biopsies from CMT1A patients. Recent studies with genetically modified Schwann cells have demonstrated that the altered expression of PMP22 modulates cell growth. Thus we hypoth...

These studies were initiated to determine whether the soluble, truncated form of the nerve growth factor (NGF) receptor arises from post-translational processing of the intact, membrane-bound receptor or from an alternatively spliced mRNA. Pulse-chase analysis of cultured primary rat Schwann cells coupled with immunoprecipitations using antibodies to the intracellular and extracellular domains ...

The mechanism of low-affinity NGF receptor (LNGFR) truncation was investigated in cultured Schwann cells. Affinity labeling of Schwann cells with 125I-NGF or metabolic labeling with 35S-cysteine showed that truncated NGF receptor (NGF-Rt) was derived from the cell surface form of the receptor. Addition of full-length, exogenous NGF receptor (M(r) = 80 kDa) to Schwann cell membranes resulted in ...