All About Multiple Sclerosis

More MS news articles for November 2002

The great vesicle controversy

Monday 4 November 2002
SFN 2002 - Day 2
Investigators: William Mobley, Bob Campenot and David Ginty
by Rabiya Tuma

For thirty years, biology students were taught that signal proteins were endocytosed at the distal end of the axon and transported back to the cell body, where the information was used to activate transcription, initiate apoptosis, or what have you. But the mechanism of retrograde transport, as this axon-to-cell body movement is called, was not a question.

That is not until, Robert (Bob) Campenot, a neurobiologist at the University of Alberta published several papers in recent years that forced everyone rethink the dogma. "The field was completely shaken up by a small lab in Alberta," David Kaplan told BioMedNet News with a bit of an amused smile. "Now everybody has to respond to Bob." And the paradigm has shifted because of it.

"We don't question that there is retrograde vesicle transport," said Campenot. "Our point is that we have found conditions under which we can generate neuronal survival that is not associated with retrograde transport of NGF - and we think that reflects the in vivo situation."

Prior to Campenot's arrival on the scene, researchers thought that retrograde transport of nerve growth factor (NGF) was required for cell survival. In fact, some still think that is the case.

Immediately following Campenot's talk this morning, David Ginty, a Howard Hughes Medical Institute investigator at Johns Hopkins University School of Medicine, presented results which he says are consistent only with vesicle-based transport. Furthermore, even though he uses very similar - but not identical - methods to Campenot, Ginty finds no evidence of NGF-independent survival; if he blocks transport of NGF and its receptor TrkA, the cells die.

Kaplan, who says that he is often called on to moderate this prickly debate both in person and in print, doesn't think either researcher is wrong. "I think it is important to avoid the word controversy. There is no controversy. Each of the groups tell us about different systems and tell us that there are multiple ways of getting signals back to the cell body that are used by neurons."

William Mobley from Stanford University, who chaired the session, agreed with Kaplan's assessment and went one step further. "I think the important attitude to have in the field right now is that these mechanisms are probably multiple. And for everyone that is proposed, one needs incredibly careful, thoughtful cell biology and biochemistry to really get to the mechanism. And I really think that is what all of our labs up to right now."

© Elsevier Science Limited 2002