Dynactin

Dynactin or Dynein activator complex is a multi-subunit protein found in eukaryotic cells that aids in bidirectional intracellular transport by binding to dynein and Kinesin 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 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. 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, DCTN2/dynamitin, DCTN3/p22/p24;(2)the Arp1 rod: Arp1/centractin, actin, CapZ; and (3) the pointed end complex: Actr10/Arp11, DCTN4/p62, DCTN5/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 microtubules to centrosomes and may play a role in synapse 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 or late endosome) through its association with β-spectrin.

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. Dynactin contributes to mitotic spindle pole focusing through its binding to NUMA. 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, zebrafish or in different fungi. Dynein and dynactin concentrate on the nuclear envelope during the prophase and facilitate nuclear envelope breakdown. Dynactin is also required for microtubule anchoring at centrosomes and centrosome integrity. Destabilization of the centrosomal pool of dynactin also causes abnormal G1 centriole separation and delayed entry into S phase, suggesting that dynactin contributes to the recruitment of important cell cycle regulators to centrosomes. In addition to transport of various organelles in the cytoplasm, dynactin also links kinesin II to organelles.