The Residents - Thundering Skies

Microtubules serve as tracks for two classes of motor proteins — namely, kinesins and dyneins. Kinesins moving along microtubules usually carry cargo such as organelles and vesicles from the center of a cell to its periphery. Dyneins are important in sliding microtubules relative to one other during the beating of cilia and flagella on the surfaces of some eukaryotic cells. Some members of the kinesin family are crucial to the transport of organelles and other cargo to nerve endings at the periphery of neurons. It is not surprising, then, that mutations in these kinesins can lead to nervous system disorders. For example, mutations in a kinesin called KIF1Bβ can lead to the most common peripheral neuropathy (weakness and pain in the hands and feet), Charcot-Marie-Tooth disease, which affects 1 in 2500 people. A glutamine-to-leucine mutation in the P-loop of the motor domain of this kinesin has been found in some affected persons. Knockout mice with a disruption of the orthologous gene have been generated. Mice heterozygous for the disruption show symptoms similar to those observed in human beings; homozygotes die shortly after birth. Mutations in other kinesin genes have been tentatively linked to a predisposition to schizophrenia. In these disorders, defects in kinesin-linked transport may impair nerve function directly, and the decrease in the activity of specific neurons may lead to other degenerative processes.