Neurotrophic fctr.retrgrd.transport

[Christopher G Winter]

Several papers published in the last couple of years have demonstrated 
that neurotrophic factors (NTFs) can be transported by sensory and motor 
neurons from the periphery to their cell bodies located in the the dorsal root 
ganglia and spinal cord, respectively. In the case of the NGF family of 
ligands, the translocation process is mediated by the low affinity NGF  
receptor, or p75.

I have several questions regarding the interpretation of this data. 
The central question is, what's the biological/physiological significance of
this phenomena? More specifically, is it a requirement that binding of NTFs
to their receptors occur at the cell body in order to generate 
an effective intracellular signal? What evidence is there for or against 
the notion that receptor activation in distal regions of the axon 
does not accomplish the task. In other words, is there even a need to 
invoke retrograde transport to explane how peripheral signals affect a 
response within the cell body? Some of the functions of NTFs may  not 
even require signalling via the the cell body.But even for those that do, 
couldn't this occur by means of intracellular diffusion of small 
molecules like Calcium?

The other set of questions I have relate to the mechanism by which 
ligands that are retrogradely transported are able to generate cytoplasmic
signals.I am not so familiar with the literature in this area, so I would 
be glad if someone could help me out on this. Does receptor mediated, 
retrograde transport of ligands occur via internalization of the receptor- 
ligand complex or without, by moving along the axon in the plane of the 
plasma membrane? If the former is the case then the ligand would  
presumeably be within a transport vesicle. How then would it generate a 
signal from 
inside a vesicle? Would such vesicles be fused with the cell membrane, 
after transport, resulting in re-secretion of the trophic factor?

I would be grateful to anyone out there who might be able to provide some 
answers to these or related questions. In lieu of answers, conjecture is 
welcome and encouraged.

Sincerely,

Christopher G. Winter
Dept.of Biochemistry
Columbia University