Dynactin

Dynactin was identified as an activity that allowed purified cytoplasmic dynein to move membrane vesicles along microtubules in vitro. It was shown to be a multiprotein complex and named "dynactin" because of its role in dynein activation. The main features of dynactin were visualized by quick-freeze, deep-etch, rotary shadow electron microscopy. It appears as a short filament, 37-nm in length, which resembles F-actin, plus a thinner, laterally oriented arm. Antibody labelling was used to map the location of the dynactin subunits. == Structure ==

Dynactin consists of three major structural domains: (1) sidearm-shoulder: DCTN1/p150Glued, DCTN2/p50/dynamitin, DCTN3/p24/p22;(2)the Arp1 filament: ACTR1A/Arp1/centractin, actin, CapZ; and (3) the pointed end complex: Actr10/Arp11, DCTN4/p62, DCTN5/p25, and DCTN6/p27. revealed that its filament contains eight Arp1 molecules, one β-actin and one Arp11. In the pointed end complex p62/DCTN4 binds to Arp11 and β-actin and p25 and p27 bind both p62 and Arp11. At the barbed end the capping protein (CapZαβ) binds the Arp1 filament in the same way that it binds actin, although with more charge complementarity, explaining why it binds dynactin more tightly than actin. The shoulder contains two copies of p150Glued/DCTN1, four copies of p50/DCTN2 and two copies of p24/DCTN3. Arp1 has been suggested as the domain for dynactin binding to membrane vesicles (such as Golgi or late endosome) through its association with β-spectrin. The pointed end complex (PEC) has been shown to be involved in selective cargo binding. PEC subunits p62/DCTN4 and Arp11/Actr10 are essential for dynactin complex integrity and dynactin/dynein targeting to the nuclear envelope before mitosis. Actr10 along with Drp1 (Dynamin related protein 1) have been documented as vital to the attachment of mitochondria to the dynactin complex. Dynactin p25/DCTN5 and p27/DCTN6 are not essential for dynactin complex integrity, but are required for early and recycling endosome transport during the interphase and regulation of the spindle assembly checkpoint in mitosis. ==Interaction with dynein==

Dynein and dynactin were reported to interact directly by the binding of dynein intermediate chains with p150Glued. The affinity of this interaction is around 3.5μM. Dynein and dynactin do not run together in a sucrose gradient, but can be induced to form a tight complex in the presence of the N-terminal 400 amino acids of Bicaudal D2 (BICD2), a cargo adaptor that links dynein and dynactin to Golgi derived vesicles. In the presence of BICD2, dynactin binds to dynein and activates it to move for long distances along microtubules. A cryo-EM structure of dynein, dynactin and BICD2 ==Functions==

Dynactin is often essential for dynein activity 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 nuclear mitotic apparatus protein (NuMA). Dynactin also targets to the kinetochore through binding between DCTN2/dynamitin and zw10 and has a role in mitotic spindle checkpoint inactivation. During prometaphase, dynactin also helps target polo-like kinase 1 (Plk1) to kinetochores through cyclin dependent kinase 1 (Cdk1)-phosphorylated DCTN6/p27, which is involved in proper microtubule-kinetochore attachment and recruitment of spindle assembly checkpoint protein Mad1. zebrafish or in different fungi. Dynein and dynactin concentrate on the nuclear envelope during the prophase and facilitate nuclear envelope breakdown via its DCTN4/p62 and Arp11 subunits. 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. == See also ==