DCTN1 Gene

The DCTN1 gene (DCTN1 stands for "Dynactin Subunit 1") is a protein-coding gene located on chromosome 2p13.1. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms.

The DCTN1 gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 10 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. Dynactin is involved in a variety of cellular functions, including ER-Golgi transport, centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis.

The dynactin subunit 1 interacts with the dynein intermediate chain by binding its domains directly to dynein. The protein binds to microtubules via a highly conserved glycine-rich cytoskeleton-associated protein domain (CAP-Gly) in its N-terminus.

Mutations in this gene cause Perry syndrome and Distal Hereditary Motor Neuronopathy, type 7b, also known as distal spinal and bulbar muscular atrophy (dSBMA).

Dynactin subunit 1" plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting dynein and binding to microtubules. Binds to both dynein and microtubules, providing a link between microtubules and dynein. It is essential for dynein alignment and for improving dynein processivity (the ability to move along a microtubule for a long distance without falling off track).

1. Caroppo P et al (2014) DCTN1 mutation analysis in families with progressive supranuclear palsy-like phenotypes. JAMA Neurol 71: 208-215.
2. Farrer MJ et al (2009) DCTN1 mutations in Perry syndrome. Nature Genet 41: 163-165.
3. Perry TL et al (1975) Hereditary mental depression and parkinsonism with taurine deficiency. Arch. Neurol 32: 108-113.
4. Perry TL et al (1990) Dominantly inherited apathy, central hypoventilation, and parkinson's syndrome: clinical, biochemical, and neuropathologic studies of 2 new cases. Neurology 40: 1882-1887.