Hereditary sensory neuropathy affects predominantly sensory nerves. Symptoms included sensation loss, decreased or absent reflexes, foot deformities and various anatomic features.
Dynein appears to be a likely suspect, the authors report. Although it is found throughout the body, Dynein plays an important role in the transport of cargo within axons, the elongated extension of nerve cells that transmit signals from one neuron to another. Dynein is crucial for survival, because mice that lack dynein or have mutations in both Dync1h copies die before birth.
Although dynein is important for the whole body, defects are found only in sensory neurons, and predominantly in hind limbs.
The key question is why" said Popko. This mutation may affect transport proteins in all neurons, but perhaps the region that is mutated is more important for the proteins that it transports in sensory neurons, whereas other regions could play a role in motor neurons. Also, mutations in different regions of this protein seem to have different effects. That may be due to differences in the cargo-binding domains.
Affected neurons in mice and in patients with sensory neuropathies have very long axons. Such neurons that transmit signals over huge distances depend on dynein, the "cargo-transporter" to carry molecules from the tip of the axon to the neurons cell bodies. If the cargo-transporter is somehow disturbed, Popko said, like in the case of mutations in Dync1h gene
|Contact: Scot Roskelley|
University of Chicago Medical Center