Cytoplasmic dynein is an enormous minus end-directed microtubule motor. Rather than existing as bare tracks, microtubules are bound by numerous microtubule-associated proteins (MAPs) that have the capacity to affect various cellular functions, including motor-mediated transport. One such MAP is She1, a dynein effector that polarizes dynein-mediated spindle movements in budding yeast. Here, we characterize the molecular basis by which She1 affects dynein, providing the first such insight into which a MAP can modulate motor motility. We find that She1 affects the ATPase rate, microtubule-binding affinity, and stepping behavior of dynein, and that microtubule binding by She1 is required for its effects on dynein motility. Moreover, we find that She1 directly contacts the microtubule-binding domain of dynein, and that their interaction is sensitive to the nucleotide-bound state of the motor. Our data support a model in which simultaneous interactions between the microtubule and dynein enables She1 to directly affect dynein motility.
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The microtubule-associated protein She1 coordinates directional spindle positioning by spatially restricting dynein activity.
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Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, USA.
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- Dynein motors help move the mitotic spindle to the division plane during cell division, with assistance from a microtubule-associated protein (MAP) called She1 in budding yeast.
- She1 plays a crucial role in keeping the spindle near the bud neck, ensuring proper segregation of chromosomes into mother and daughter cells during anaphase.
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Modeling a disease-correlated tubulin mutation in budding yeast reveals insight into MAP-mediated dynein function.
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Mutations in the genes that encode α- and β-tubulin underlie many neurological diseases, most notably malformations in cortical development. In addition to revealing the molecular basis for disease etiology, studying such mutations can provide insight into microtubule function and the role of the large family of microtubule effectors. In this study, we use budding yeast to model one such mutation-Gly436Arg in α-tubulin, which is causative of malformations in cortical development-in order to understand how it impacts microtubule function in a simple eukaryotic system.
View Article and Find Full Text PDFShe1 affects dynein through direct interactions with the microtubule and the dynein microtubule-binding domain.
Nat Commun
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Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, 80523, USA.
Cytoplasmic dynein is an enormous minus end-directed microtubule motor. Rather than existing as bare tracks, microtubules are bound by numerous microtubule-associated proteins (MAPs) that have the capacity to affect various cellular functions, including motor-mediated transport. One such MAP is She1, a dynein effector that polarizes dynein-mediated spindle movements in budding yeast.
View Article and Find Full Text PDFMicrotubule cross-linking activity of She1 ensures spindle stability for spindle positioning.
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Biology Department, University of Massachusetts, Amherst, MA
Dynein mediates spindle positioning in budding yeast by pulling on astral microtubules (MTs) from the cell cortex. The MT-associated protein She1 regulates dynein activity along astral MTs and directs spindle movements toward the bud cell. In addition to localizing to astral MTs, She1 also targets to the spindle, but its role on the spindle remains unknown.
View Article and Find Full Text PDFStopped in its tracks: negative regulation of the dynein motor by the yeast protein She1.
Bioessays
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Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA.
How do cells direct the microtubule motor protein dynein to move cellular components to the right place at the right time? Recent studies in budding yeast shed light on a new mechanism for directing dynein, involving the protein She1. She1 restricts where and when dynein moves the nucleus and mitotic spindle. Experiments with purified proteins show that She1 binds to microtubules and inhibits dynein by stalling the motor on its track.
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