DCTN1

The DCTN1 gene provides instructions for making a protein called dynactin-1. At least two different versions of this protein are produced in cells. The two versions differ in size; the larger version is called p150-glued, and the smaller version is called p135.

Dynactin-1 interacts with several other proteins to form a complex (a group of proteins that work together) called dynactin. The p150-glued version of dynactin-1 is the largest component (subunit) of the dynactin complex. This complex plays a critical role in cell division and the transport of materials within cells. To carry out these roles, the p150-glued subunit binds to a molecular motor called dynein and to a track-like system of small tubes called microtubules. The dynactin complex, dynein, and microtubules work together like a conveyer belt to move materials within cells.

Researchers believe that the dynactin complex is particularly important for the proper function of axons, which are specialized extensions of nerve cells. Axons transmit impulses from nerve to nerve and from nerves to muscles. Axons can be quite long; some are more than 3 feet in length. The dynactin complex is a critical part of a rapid transport system that supplies axons with materials to keep them healthy and functioning efficiently.

amyotrophic lateral sclerosis - increased risk from variations of the DCTN1 gene

Researchers have identified a few mutations in the DCTN1 gene that may increase the risk of developing amyotrophic lateral sclerosis. These mutations replace one of the protein building blocks (amino acids) used to make dynactin-1 with an incorrect amino acid. These mutations likely alter the 3-dimensional shape of dynactin-1, which may impair its binding with microtubules.

It is unclear how DCTN1 mutations might increase susceptibility to amyotrophic lateral sclerosis. Impaired binding between the p150-glued version of dynactin-1 and microtubules may slow the transport of materials needed for the proper function of axons in motor neurons. Motor neurons are specialized nerve cells in the brain and spinal cord that control muscle movement. The decline and death of motor neurons is a characteristic feature of amyotrophic lateral sclerosis.

other disorders - associated with the DCTN1 gene

Researchers have identified one mutation that causes a nervous system disorder called lower motor neuron disease. This disorder affects motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. Signs and symptoms of lower motor neuron disease first appear in early adulthood and include breathing difficulties and progressive weakness of muscles in the face and hands. Muscle weakness in the feet and legs develops later. The mutation that causes this disorder changes one of the protein building blocks (amino acids) used to make dynactin-1. Specifically, the amino acid glycine is replaced by the amino acid serine at protein position 59 (written as Gly59Ser). It is unclear how this mutation causes lower motor neuron disease. It may disturb interactions between the dynactin complex and microtubules, which disrupts transport activities and impairs the function of axons in motor neurons.

One DCTN1 mutation is associated with a brain disorder called frontotemporal dementia, which occurs in mid to late adulthood. This disorder is characterized by behavioral changes such as impulsiveness and outbursts of frustration. Changes in language function can also occur, such as problems using the correct word and difficulties in reading. The DCTN1 mutation associated with this disorder switches one amino acid in dynactin-1. Specifically, the amino acid arginine is replaced with the amino acid lysine at protein position 1101 (written as Arg1101Lys). This mutation likely alters the 3-dimensional shape of dynactin-1, which may impair its binding with microtubules. The role of this mutation in frontotemporal dementia is unclear. Impaired binding between the p150-glued version of dynactin-1 and microtubules may slow the transport of materials needed for the proper function of axons and efficient transmission of nerve impulses.