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Home > A. Molecular pathology > DCTN1



Sunday 22 January 2006

Cytoplasmic dynein is a microtubule-based biologic motor protein. Dyneins were initially discovered as enzymes that couple ATP hydrolysis to provide a force for cellular motility in eukaryotic cilia and flagella.

A distinct cytoplasmic form of dynein (MIM.600112) was subsequently characterized and thought to be responsible for the intracellular retrograde motility of vesicles and organelles along microtubules.

A large macromolecular complex, dynactin, is required for the cytoplasmic dynein-driven movement of organelles along microtubules.

Dynactin is composed of 10 distinct polypeptides of 150, 135, 62, 50 (DCTN2) (MIM.607376), 45, 42, 37, 32, 27, and 24 kD, with a combined mass of 10 million daltons.

The largest polypeptide of the dynactin complex, p150(Glued), binds directly to microtubules and to cytoplasmic dynein.

The binding of dynactin to dynein is critical for neuronal function, as antibodies that specifically disrupt this binding block vesicle motility along microtubules in extruded squid axoplasm.

The dynein-dynactin interaction is probably a key component of the mechanism of axonal transport of vesicles and organelles.


- germline mutations in slowly progressive, autosomal dominant form of lower motor neuron disease without sensory symptoms (MIM.607641)

- variants in susceptibility to amyotrophic lateral sclerosis (MIM.105400)

Animal models

Further evidence for a critical role for dynactin in vivo comes from the analysis of mutations in the homologous gene in Drosophila. Mutant alleles of the ’glued’ gene induced disruption of the neurons of the optic lobe and compound eye in heterozygotes; null mutations are lethal.

See also

- ALS genes