ISSN 1062-3604, Russian Journal of Developmental Biology, 2006, Vol. 37, No. 5, pp. 267–281. © Pleiades Publishing, Inc., 2006. Original Russian Text © A.V. Burakov, E.S. Nadezhdina, 2006, published in Ontogenez, 2006, Vol. 37, No. 5, pp. 323–339. 267 STRUCTURE OF DYNEIN AND DYNACTIN MOLECULES AND THEIR INTERACTION WITH OTHER PROTEINS Dyneins are one of the two known families of pro- teins motors that move load along the microtubules: dyneins and kinesins. Dyneins hydrolyze ATP and pro- duce a force directed to the minus-end of microtubules. There are approximately 15 forms of dynein in verte- brates, most of which are “axonemic”, i.e. involved in the movement of cilia and flagellae. Only two forms of dynein are “cytoplasmic”. One of them was initially called MAP1c (protein 1C associated with microtu- bules) (Paschal et al., 1987) and later received the name of cytoplasmic dynein 1. Dynein 1 is abundantly expressed in the cells and fulfils many functions: trans- port of cell organelles, some aspects of chromosome behavior, orientation of mitotic spindle, translocation of nucleus, and cell locomotion, which will be consid- ered in detail below. Another form of cytoplasm dynein, dynein 1b or dynein 2, has very restricted functions (Pazour et al., 1999). In tissues, it occurs almost exclusively in the cells with cilia and in different mobile and immobile ciliary structures (Mikami et al., 2002). In all likeli- hood, dynein 2 is responsible for the transport from the distal to the proximal end of axonemic structures, which is essential for the removal of used components of cilia or flagellae. In addition, rapid retrograde trans- port of the protein transducin in the retina in response to light appears to be realized with the help of dynein 2 (Sokolov et al., 2002). In any case, the cytoplasmic dynein 1 plays the main role in the cell cytoplasm and we will discuss it below. Structure of dynein molecule. Cytopasmic dynein (DC) is a multisubunit complex (Fig. 1a). Its total molecular mass reaches 1Mda. The complex includes two dynein cytoplasmic heavy chains (DCHC or DHC), 530 kDa each, three dynein cytoplasmic intermediate chains (DCIC or DIC), 74 kDa each, four dynein cyto- plasmic light intermediate chains (DCLIC or DLIC), 55 kDA each, and several dynein cytoplasmic light chains (DCLC or DLC), 8 to 20 kDa each (Hirokawa, 1998). Dynein belongs to the class of ATPase Associated with diverse cellular Activities (AAA-proteins). Six AAA-domains, the first four of which are capable of hydrolyzing ATP, are localized in each motor domain in the composition of DHC. Domains AAA1 and AAA3, whose affinity to ATPase is higher than in all others, usually act as ATPases. AAA-domains form a toroidal structure and there is an eminence of 325 amino acids, 15 nm long, between the fourth and fifth AAA-domains, at the end of which the site of binding to microtubules is located. Hydrolysis of ATP leads to rotation of the REVIEWS Dynein and Dynactin as Organizers of the System of Cell Microtubules A. V. Burakov a and E. S. Nadezhdina b a Belozersky Research Institute of Physicochemical Biology, Moscow State University, Leninskie Gory, Moscow, 119992 Russia b Institute of Protein Synthesis, Russian Academy of Sciences, ul. Vavilova 34, Moscow, 117334 Russia E-mail: antburakov@mail.ru Received December 12, 2005; in final form, February 13, 2006 Abstract—A review of the role of the microtubule motor dynein and its cofactor dynactin in the formation of a radial system of microtubules in the interphase cells and of mitotic spindle. Deciphering of the structure, func- tions, and regulation of activity of dynein and dynactin promoted the understanding of mechanisms of cell and tissue morphogenesis, since it turned out that these cells help the cell in finding its center and organize micro- tubule-determined anisotropy of intracellular space. The structure of dynein and dynactin molecules has been considered, as well as possible pathways of regulation of the dynein activity and the role of dynein in transport of cell components along the microtubules. Attention has also been paid to the functions of dynein and dynactin not related directly to transport: their involvement in the formation of an interphase radial system of microtu- bules. This system can be formed by self-organization of microtubules and dynein-containing organelles or via organization of microtubules by the centrosome, whose functioning requires dynein. In addition, dynein and dynactin are responsible for cell polarization during its movement, as well as for the position of nucleus, cen- trosomes, and mitotic spindle in the cell. DOI: 10.1134/S1062360406050018 Key words: microtubules, dynein, dynactin, centrosome, mitosis, cell shape.