PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcellbiolHomeThe Rockefeller University PressThis articleEditorsContactInstructions for AuthorsThis issue
 
J Cell Biol. 2010 April 5; 189(1): 6.
PMCID: PMC2854385
In This Issue

Ataxia's double hit

An external file that holds a picture, illustration, etc.
Object name is jcb.1891iti2fig1.jpg

A fly larva carrying a faulty human β-III–spectrin gene hoists its paralyzed hindquarters, a maneuver called a tail flip.

The neurodegenerative disease spinocerebellar ataxia type 5 (SCA5) damages nerve cells in two ways. Lorenzo et al. report that the defective protein responsible for the disease cuts the number of synaptic terminals and snarls traffic inside neurons.

SCA5 results from a faulty gene for β-III–spectrin. The disease targets the cerebellum's Purkinje cells, which control coordination. How the mutant protein damages neurons remains uncertain. β-III–spectrin stabilizes synapses, suggesting that synapse deterioration might doom the cells. But the protein also helps the adapter protein dynactin hitch cargoes to dynein motors, pointing to a disruption of intracellular transportation.

The team found support for both mechanisms. They engineered fruit flies to carry a mutated β-III–spectrin gene. Fly larvae with the mutated gene had paralyzed tails. At the neuromuscular junctions where nerves and muscles meet, the larvae showed fewer presynaptic terminals.

The researchers next tracked the movement of synaptic vesicles in axons from the animals. Vesicles from flies that made the faulty β-III–spectrin were slower and more likely to change direction, and thus traveled shorter distances. Other neurodegenerative diseases, including Alzheimer's disease and amyotrophic lateral sclerosis, involve faulty transport, and the results indicate that SCA5 does too.

The two mechanisms might have a common link, the researchers suggest. The complex containing β-III–spectrin, dynactin, and dynein might not just haul cargoes. At the synapse it might snag microtubules that strengthen the membrane and prevent degeneration.

References


Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press