Off the rails: axonal cargoes on the road to nowhere

Abstract

EMBO J (2013) 32 10, 1352–1364. doi:; DOI: 10.1038/emboj.2013.59

The importance of the microtubule cytoskeleton for neuronal development, organization and maintenance is reflected in the finding that mutations in various tubulin genes cause a range of nervous system abnormalities. Mutations in the β-tubulin isotype-III gene, TUBB3, alter the interaction between microtubules and motor proteins leading to neurological impairments. Niwa et al (2013) now report that TUBB3 mutations lead to neuronal defects by impairing axonal transport.

Figure 1

Model showing how tubulin mutations affect kinesin-dependent axonal transport. In the axon, kinesins normally transport mitochondria and vesicles by walking along the microtubule lattice towards the microtubule plus-ends. However, TUBB3 mutations that disrupt the negative charge at the microtubule—motor interface impair either the attachment or the docking of kinesins on the microtubules. This leads to disruption of axonal transport and consequently to the development of neurodegenerative diseases.