In molecular biology, DCTN6 is that subunit of the

dynactin Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 ( Arp1). Discovery Dynactin was identified as an activity that allow ...

protein complex that is encoded by the p27 gene. Dynactin is the essential component for microtubule-based cytoplasmic dynein motor activity in

intracellular transport Intracellular transport is the movement of vesicles and substances within a cell. Intracellular transport is required for maintaining homeostasis within the cell by responding to physiological signals. Proteins synthesized in the cytosol are dis ...

of a variety of cargoes and organelles.

Identification and structure

DCTN6 was first identified and cloned as a subunit of the "pointed-end complex" of

through biochemical purification. X-ray crystal structure revealed that dynactin p27 forms an unusual left handed β-helix (LβH) domain, and its phosphorylation site T186 is in C-terminal disordered segment.

Function

In intracellular transport

Dynactin p27 forms a hetero-dimer with the other dynactin pointed-end complex subunit p25/DCTN5 in 1:1 ratio, and it is essential for p25 stability since they are co-knockdown by p27 RNAi. However, both p27 and p25 are not required for 19S dynactin complex integrity verified by velocity sedimentation. p27/DCTN6 and other dynactin pointed-end complex subunits (Arp11/ Actr10, p62/

DCTN4 Dynactin subunit 4 is a protein that in humans is encoded by the DCTN4 gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...

, and p25/

DCTN5 Dynactin 5 (p25) is a protein that in humans is encoded by the DCTN5 gene. This gene encodes a subunit of dynactin, a component of the cytoplasmic dynein motor machinery involved in minus-end-directed transport. The encoded protein is a componen ...

) have been suggested to be involved in dynactin binding to specific intracellular cargoes. Co-depletion of dynactin p27 and p25 by p27 RNAi affects dynactin binding to endomembrane, and early and recycling

endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...

movements are impaired, suggesting that p27/p25 form a selective endomembrane cargo-targeting module.

In mitosis

In mitosis, unlike dynactin or dynein perturbation that causes

mitotic spindle In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...

disarrangement and mitotic arrest, dynactin p27/p25 depletion does not affect mitotic spindle formation, pole focusing or dynein/dynactin targeting to

kinetochore A kinetochore (, ) is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and ...

s. However, dynactin p27/p25 are required for normal

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

alignment, kinetochore-microtubule interaction, and proper timing of anaphase onset. Dynactin p27 C-terminal T186 residue is phosphorylated by

cyclin-dependent kinase 1 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in ...

(

Cdk1 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in t ...

) in mitosis and helps target polo-like kinase 1 (

Plk1 Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the ''PLK1'' ( polo-like kinase 1) gene. Structure PLK1 consists of 603 am ...

) to kinetochores during

prometaphase Prometaphase is the phase of mitosis following prophase and preceding metaphase, in eukaryote, eukaryotic Somatic (biology), somatic Cell (biology), cells. In prometaphase, the nuclear membrane breaks apart into numerous "membrane vesicles", ...

. This activity facilitates phosphorylation of important downstream kinetochore targets (such as tension-sensing 3F3/2 phospho-epitope) of

, which is important for recruitment of spindle assembly checkpoint proteins such as

Mad1 Mad1 is a non-essential protein which in yeast has a function in the spindle assembly checkpoint (SAC). This checkpoint monitors chromosome attachment to spindle microtubules and prevents cells from starting anaphase until the spindle is built up ...

and proper kinetochore-microtubule attachment.

References

{{Reflist Human proteins Motor proteins