Dynactin consists of many subunits of which the p150Glued protein (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 p150Glued. 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. 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. 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.
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 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. 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 via its DCTN4/p62 and Arp11 subunits. 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.
^Uetake Y, Terada Y, Matuliene J, Kuriyama R (May 2004). "Interaction of Cep135 with a p50 dynactin subunit in mammalian centrosomes". Cell Motil. Cytoskeleton. 58 (1): 53–66. doi:10.1002/cm.10175. PMID14983524.
^Karki S, Tokito MK, Holzbaur EL (February 2000). "A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1". J. Biol. Chem. 275 (7): 4834–9. doi:10.1074/jbc.275.7.4834. PMID10671518.
^Holleran, EA; Ligon, LA; Tokito, M; Stankewich, MC; Morrow, JS; Holzbaur, E.L. F. (2001). "βIII Spectrin Binds to the Arp1 Subunit of Dynactin". The Journal of Biological Chemistry. 276 (39): 36598–36605. doi:10.1074/jbc.M104838200. PMID11461920.
^Muresan, V; Stankewich, MC; Steffen, W; Morrow, JS; Holzbaur, EL; Schnapp, BJ (2001). "Dynactin-Dependent, Dynein-Driven Vesicle Transport in the Absence of Membrane Proteins". Molecular Cell. 7 (1): 173–183. doi:10.1016/S1097-2765(01)00165-4. PMID11172722.
^Salina, D; Bodoor, K; Eckley, DM; Schroer, TA; Rattner, JB; Burke, B (Jan 11, 2002). "Cytoplasmic dynein as a facilitator of nuclear envelope breakdown.". Cell. 108 (1): 97–107. doi:10.1016/S0092-8674(01)00628-6. PMID11792324.
^Zhang, J; Wang, L; Zhuang, L; Huo, L; Musa, S; Li, S; Xiang, X (July 2008). "Arp11 affects dynein-dynactin interaction and is essential for dynein function in Aspergillus nidulans.". Traffic (Copenhagen, Denmark). 9 (7): 1073–87. doi:10.1111/j.1600-0854.2008.00748.x. PMID18410488.
^ abcYeh, TY; Quintyne, NJ; Scipioni, BR; Eckley, DM; Schroer, TA (October 2012). "Dynactin's pointed-end complex is a cargo-targeting module.". Molecular Biology of the Cell. 23 (19): 3827–37. doi:10.1091/mbc.E12-07-0496. PMID22918948.
^Zhang, J; Yao, X; Fischer, L; Abenza, JF; Peñalva, MA; Xiang, X (Jun 27, 2011). "The p25 subunit of the dynactin complex is required for dynein-early endosome interaction.". The Journal of Cell Biology. 193 (7): 1245–55. doi:10.1083/jcb.201011022. PMID21708978.
^ abYeh, TY; Kowalska, AK; Scipioni, BR; Cheong, FK; Zheng, M; Derewenda, U; Derewenda, ZS; Schroer, TA (Apr 3, 2013). "Dynactin helps target Polo-like kinase 1 to kinetochores via its left-handed beta-helical p27 subunit.". The EMBO Journal. 32 (7): 1023–35. doi:10.1038/emboj.2013.30. PMID23455152.
^Karki Sher; Holzbaur Erika LF (1 February 1999). "Cytoplasmic dynein and dynactin in cell division and intracellular transport". Current Opinion in Cell Biology. 11 (1): 45–53. doi:10.1016/S0955-0674(99)80006-4. PMID10047518.
^Xiang, X; Han, G; Winkelmann, DA; Zuo, W; Morris, NR. (2000). "Dynamics of cytoplasmic dynein in living cells and the effect of a mutation in the dynactin complex actin-related protein Arp1". Curr Biol. 10 (10): 603–6. doi:10.1016/S0960-9822(00)00488-7. PMID10837229.