Biology Reference
In-Depth Information
Further understanding of the mechanism by which Wld
S
prolongs the survival of
severed distal axon stumps should be an excellent way to shed light on the nature
of anterograde axon survival signaling.
X. SUMMARY: AXONAL TRANSPORT AND AXON
SURVIVAL SIGNALING
This chapter emphasizes that axonal proteins are not all equal in their essential
nature, their transport mechanisms, their half-lives, and their capacity for local
synthesis. Essential axonal proteins fall into a surprisingly narrow list of cate-
gories, while those that are dispensable for axon survival are not necessarily those
we might have expected. There is an enormous range of protein half-lives, and
some proteins will have difficulty making it to the ends of long axons unless there
are mechanisms to stabilize them during transport or to synthesize them locally.
Functionally, we can find clues to which proteins limit axon survival
from molecular genetic studies. However, an equally promising area to explore
is the axonal roles of signaling pathways that control survival in other cell
types, as these same pathways have axonal functions but may be subject to
different control mechanisms. Intracellular transport over such long distances
is unique to axons and while this poses problems for delivering essential cargoes,
it also provides a unique mechanism for regulating death programs. Long-range
survival signaling and axonal transport may be two ways of looking at the same
thing.
Acknowledgments
This chapter reflects memorable presentations and discussions with many colleagues in addition to
the cited publications. These include but are not limited to Christine Beattie, Scott Brady, Anthony
Brown, Felipe Court, James Fawcett, Marc Freeman, Paul Glynn, Larry Goldstein, Georg Haase,
Peter Hollenbeck, Christine Holt, Erika Holzbaur, Keith Martin, Chris Miller, Thomas Misgeld,
Hugh Perry, Evan Reid, Richard Ribchester, Tom Schwarz, Zu-Hang Sheng, Aviva Tolkovsy, Jeff
Twiss, Xinnan Wang, and Dianna Willis. I am equally grateful to present former members of the
Coleman laboratory for open and constructive discussions on many topics related to this chapter.
I am also grateful to Hilda Tsang for provision of a literature summary of hereditary spastic paraplegia
that contributed to Tables 5.1 and 5.2. The author is funded by the Biotechnology and Biological
Sciences Research Council (BBSRC).
References
Adalbert, R., Nogradi, A., Babetto, E., Janeckova, L., Walker, S. A., Kerschensteiner, M.,
Misgeld, T., and Coleman, M. P. (2009). Severely dystrophic axons at amyloid plaques remain
continuous and connected to viable cell bodies.
Brain 132, 402-416.
