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Dynactin

Dynactin

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Dynactin or Dynein activator complex is a multi-subunit
Protein subunit
In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...

 protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 found in eukaryotic cells that aids in bidirectional intracellular transport by binding to dynein
Dynein
Dynein is a motor protein in cells which converts the chemical energy contained in ATP into the mechanical energy of movement. Dynein transports various cellular cargo by "walking" along cytoskeletal microtubules towards the minus-end of the microtubule, which is usually oriented towards the cell...

 and Kinesin
Kinesin
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule filaments, and are powered by the hydrolysis of ATP . The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular...

 II and linking them to the organelle or vesicle to be transported.

Structure and mechanism of action


Dynactin consists of many subunits of which the p150Glued doublet (encoded by the DCTN1
DCTN1
Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.- Function :This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein...

 gene) is the largest and has been found to be essential for function. This structure of dynactin is highly conserved in vertebrates. There are three isoforms encoded by a single p150Glued gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.
The dynactin complex visualized by deepetch electron microscopy appears as a short filament 37-nm in length, which resembles F-actin, plus a thinner, laterally oriented filament that terminates in two globular heads. The dynactin complex consists of three major structural domains: (1) sidearm-shoulder: DCTN1
DCTN1
Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.- Function :This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein...

, DCTN2
DCTN2
Dynactin subunit 2 is a protein that in humans is encoded by the DCTN2 gene.-Further reading:...

/dynamitin, DCTN3
DCTN3
Dynactin subunit 3 is a protein that in humans is encoded by the DCTN3 gene.-Further reading:...

/p22/p24;(2)the Arp1 rod: Arp1/centractin
Centractin
Centractin also known as ARP1 is a protein found in the centrosome and is a homologue of the eukaryotic protein actin. ARP1 forms a 37 nm filament-like structure and is the core of the dynactin complex, an essential activator of cytoplasmic dynein-driven vesicle movement. It only exists in...

, actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

, CapZ
CapZ
CapZ is a protein that caps the barbed end of actin filaments in muscle cells. It is located in the muscle Z band....

; and (3) the pointed end complex: Actr10/Arp11, DCTN4/p62, DCTN5
DCTN5
Dynactin 5 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 component of the pointed-end subcomplex and is thought to bind...

/p25, and DCTN6/p27.
Dynactin interacts with dynein directly by the binding of dynein intermediate chains with the p150Glued doublet.
DCTN2 (dynamitin) is also involved in anchoring microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...

s to centrosomes and may play a role in synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

 formation during brain development. DCTN4 (p62) binds directly to the Arp1 subunit of dynactin. Arp1 has been shown as the domain for dynactin binding to membrane vesicles (such as Golgi
Golgi
Golgi may refer to:*Camillo Golgi , Italian physician and scientist after which the following terms are named:**Golgi apparatus , an organelle in the eukaryotic cell...

 or late endosome) through its association with β-spectrin
Spectrin
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure...

.

Functions


Dynactin is often essential for dynein activity and can be thought of as a "dynein receptor" that modulates binding of dynein to cell organelles which are to be transported along microtubules.
Dynactin also enhances the processivity of cytoplasmic dynein  and kinesin-2 motors.
Dynactin is involved in various processes like chromosome alignment and spindle organization in cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...

. Dynactin contributes to mitotic spindle pole focusing through its binding to NUMA
Numa
Numa may refer to:* Numa Pompilius, legendary second king of Rome* Numa Morikazu, Meiji era Japanese politician* Numa, Iowa, U.S. town* The Numa Numa Internet meme* The Northern Paiute people...

. Dynactin also targets to the kinetochore through binding between DCTN2/dynamitin and zw10 and has a role in mitotic spindle checkpoint inactivation. In addition, dynactin has been shown to play an essential role in maintaining nuclear position in Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

, zebrafish  or in different fungi. Dynein and dynactin concentrate on the nuclear envelope
Nuclear envelope
A nuclear envelope is a double lipid bilayer that encloses the genetic material in eukaryotic cells. The nuclear envelope also serves as the physical barrier, separating the contents of the nucleus from the cytosol...

 during the prophase
Prophase
Prophase, from the ancient Greek πρό and φάσις , is a stage of mitosis in which the chromatin condenses into a highly ordered structure called a chromosome in which the chromatin becomes visible. This process, called chromatin condensation, is mediated by the condensin complex...

 and facilitate nuclear envelope breakdown.
Dynactin is also required for microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...

 anchoring at centrosomes and centrosome integrity. Destabilization of the centrosomal pool of dynactin also causes abnormal G1 centriole
Centriole
A Centriole is a barrel-shaped cell structure found in most animal eukaryotic cells, though it is absent in higher plants and most fungi. The walls of each centriole are usually composed of nine triplets of microtubules...

 separation and delayed entry into S phase, suggesting that dynactin contributes to the recruitment of important cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

regulators to centrosomes. In addition to transport of various organelles in the cytoplasm, dynactin also links kinesin II to organelles.