Kinesin II is a heterotrimeric plus end-directed microtubule motor responsible for the anterograde movement of organelles in various cell types. Despite substantial literature concerning the types of organelles that kinesin II transports, the question of how this motor associates with cargo organelles remains unanswered. To address this question, we have used Xenopus laevis melanophores as a model system. Through analysis of kinesin II-mediated melanosome motility, we have determined that the dynactin complex, known as an anchor for cytoplasmic dynein, also links kinesin II to organelles. Biochemical data demonstrates that the putative cargo-binding subunit of Xenopus kinesin II, Xenopus kinesin II-associated protein (XKAP), binds directly to the p150Glued subunit of dynactin. This interaction occurs through aa 530-793 of XKAP and aa 600-811 of p150Glued. These results reveal that dynactin is required for transport activity of microtubule motors of opposite polarity, cytoplasmic dynein and kinesin II, and may provide a new mechanism to coordinate their activities.
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http://dx.doi.org/10.1083/jcb.200210066 | DOI Listing |
bioRxiv
October 2024
University of Michigan, Department of Molecular, Cellular, and Developmental Biology, Ann Arbor, MI 48109.
Cytoplasmic dynein-1 (dynein), the primary retrograde motor in most eukaryotes, supports the movement of hundreds of distinct cargos, each with specific trafficking requirements. To achieve this functional diversity, dynein must bind to the multi-subunit complex dynactin and one of a family of cargo adaptors to be converted into an active, processive motor complex. Very little is known about the dynamic processes that promote the formation of this complex.
View Article and Find Full Text PDFJ Cell Biol
November 2024
Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Nuclear migration is critical for the proper positioning of neurons in the developing brain. It is known that bidirectional microtubule motors are required for nuclear transport, yet the mechanism of the coordination of opposing motors is still under debate. Using mouse cerebellar granule cells, we demonstrate that Nesprin-2 serves as a nucleus-motor adaptor, coordinating the interplay of kinesin-1 and dynein.
View Article and Find Full Text PDFJ Virol
July 2024
Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Herpesvirus assembly requires the cytoplasmic association of large macromolecular and membrane structures that derive from both the nucleus and cytoplasmic membrane systems. Results from the study of human cytomegalovirus (HCMV) in cells where it organizes a perinuclear cytoplasmic virus assembly compartment (cVAC) show a clear requirement for the minus-end-directed microtubule motor, dynein, for virus assembly. In contrast, the assembly of herpes simplex virus -1 (HSV-1) in epithelial cells where it forms multiple dispersed, peripheral assembly sites is only mildly inhibited by the microtubule-depolymerizing agent, nocodazole.
View Article and Find Full Text PDFEur J Cell Biol
September 2024
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg 40530, Sweden. Electronic address:
Chaperonin Containing Tailless complex polypeptide 1 (CCT) is a molecular chaperone composed of eight distinct subunits that can exist as individual monomers or as components of a double oligomeric ring, which is essential for the folding of actin and tubulin and other substrates. Here we assess the role of CCT subunits in the context of cell cycle progression by individual subunit depletions upon siRNA treatment in mammalian cells. The depletion of individual CCT subunits leads to variation in the distribution of cell cycle phases and changes in mitotic index.
View Article and Find Full Text PDFCell Mol Life Sci
May 2024
Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland.
The endocytic adaptor protein 2 (AP-2) complex binds dynactin as part of its noncanonical function, which is necessary for dynein-driven autophagosome transport along microtubules in neuronal axons. The absence of this AP-2-dependent transport causes neuronal morphology simplification and neurodegeneration. The mechanisms that lead to formation of the AP-2-dynactin complex have not been studied to date.
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