Disease relevance of dynein

• Animals homozygous for loss-of-function mutations in dli-1 exhibit stochastic failed divisions in late larval cell lineages, resulting in zygotic sterility. dli-1 is required for dynein function during mitosis [1].

High impact information on dynein

• C. elegans contains a microtubule binding protein that resembles both dynein and kinesin [2].
• One candidate for a mitotic motor is dynein, a large multimeric enzyme which can move along microtubules toward their slow growing end [3].
• Using antibodies that recognize subunits of cytoplasmic dyneins, we show here that during mitosis, cytoplasmic dynein antigens concentrate near the kinetochores, centrosomes and spindle fibres of HeLa and PtK1 cells, whereas at interphase they are distributed throughout the cytoplasm [3].
• Antibodies raised against cytoplasmic dyneins have shown localization of dynein antigens to the mitotic spindles in Caenorhabditis elegans embryos (Lye et al., personal communication) and punctate cytoplasmic structures in Dictyostelium amoebae [3].
• In Caenorhabditis elegans, the partitioning proteins (PARs), microfilaments (MFs), dynein, dynactin, and a nonmuscle myosin II all localize to the cortex of early embryonic cells [4].

Biological context of dynein

• Cytoplasmic dynein is localized to kinetochores during mitosis [3].
• As neither nematodes nor higher plants have motile cilia or flagella at any stage of their life cycles, these DLC homologues presumably must function within the cytoplasm where they may represent previously unrecognized components of cytoplasmic dynein [5].
• lis-1 is required for dynein-dependent cell division processes in C. elegans embryos [6].
• This gene is composed of 15 exons and 14 relatively short introns, and it has significant homology to the other dynein heavy chains in the databases [7].
• As with other dynein heavy chains that have been sequenced to date, it contains four GXXGXGK(S/T) motifs that form part of a consensus sequence for the nucleotide triphosphate-binding domains [7].

Anatomical context of dynein

• Thus, we propose that the class DHC1b cytoplasmic dynein, CHE-3, is specifically responsible for the retrograde transport of the anterograde motor, kinesin-II, and its cargo within sensory cilia, but not within dendrites [8].
• Therefore, cytoplasmic dynein is required for multiple aspects of MTOC positioning in the one cell stage C. elegans embryo [9].
• The M(r) = 8,000 and 11,000 outer arm dynein light chains from Chlamydomonas flagella have cytoplasmic homologues [5].
• This isoform of dynein shows temporally and spatially restricted expression in ciliated sensory neurons, and mutants show progressive developmental defects of the chemosensory cilia [10].
• IFT has been defined as the mechanism by which protein raft components (also called IFT particles) are displaced between the flagellum and the plasma membrane in the anterograde direction by kinesin-II and in the retrograde direction by cytoplasmic dynein 1b [11].

Associations of dynein with chemical compounds

• We show that the LIC subunit copurifies with cDHC1b during flagellar isolation, dynein extraction, sucrose density centrifugation, and immunoprecipitation [12].

Physical interactions of dynein

• NudC forms a biochemical complex with components of the dynein/dynactin complex and is suggested to play a role in translocation of nuclei in proliferating neuronal progenitors as well as in migrating neurons in culture [13].

Other interactions of dynein

• In let-99 one-cell embryos, the nuclear-centrosome complex exhibits a hyperactive oscillation that is dynein dependent, instead of the normal anteriorly directed migration and rotation of the nuclear-centrosome complex [14].
• These forces, which appear to be mediated by dynein and dynactin, produce changes in the shape and orientation of mitotic spindles [4].
• To test the hypothesis that the minus end-directed microtubule motor protein, cytoplasmic dynein, drives this retrograde transport pathway, we visualized movement of kinesin-II and its cargo along dendrites and cilia in a che-3 cytoplasmic dynein mutant background, and observed an inhibition of retrograde transport in cilia but not in dendrites [8].
• Many cargoes link to dynein via interactions between dynactin and vesicle-associated spectrin [15].
• We have investigated the role of cytoplasmic dynein in microtubule organizing center (MTOC) positioning using RNA-mediated interference (RNAi) in Caenorhabditis elegans to deplete the product of the dynein heavy chain gene dhc-1 [9].

Analytical, diagnostic and therapeutic context of dynein

• Digital time-lapse video microscopy was used to determine that RNAi-treated embryos exhibited nuclear positioning defects in early embryonic cell division similar to those reported for dynein/dynactin depletion [16].

References