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Background

Cytoplasmic dynein motility along microtubules is critical for diverse cellular processes ranging from vesicular transport to nuclear envelope breakdown to mitotic spindle alignment. In yeast, we have proposed a regulated-offloading model to explain how dynein motility drives microtubule sliding along the cortex, powering transport of the nucleus into the mother-bud neck [1, 2]: the dynein regulator She1 limits dynein offloading by gating the recruitment of dynactin to the astral microtubule plus end, a prerequisite for offloading to the cortex. However, whether She1 subsequently affects cortically anchored dynein activity during microtubule sliding is unclear.

Results

Using single-molecule motility assays, we show that She1 strongly inhibits dynein movement along microtubules, acting directly on the motor domain in a manner independent of dynactin. She1 has no effect on the motility of either Kip2, a kinesin that utilizes the same microtubule track as dynein, or human kinesin-1, demonstrating the specificity of She1 for the dynein motor. At single-molecule resolution, She1 binds tightly to and exhibits diffusional behavior along microtubules. Diffusive She1 collides with and pauses motile dynein motors, prolonging their attachment to the microtubule. Furthermore, Aurora B/Ipl1 directly phosphorylates She1, and this modification appears to enhance the diffusive behavior of She1 along microtubules and its potency against dynein. In cells, She1 dampens productive microtubule-cortex interactions specifically in the mother compartment, polarizing spindle movements toward the bud cell.

Conclusions

Our data reveal how inhibitory microtubule-associated proteins selectively regulate motor activity to achieve unidirectional nuclear transport and demonstrate a direct link between cell-cycle machinery and dynein pathway activity."xsd:string
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http://purl.uniprot.org/citations/23142046http://purl.uniprot.org/core/author"Lee W.L."xsd:string
http://purl.uniprot.org/citations/23142046http://purl.uniprot.org/core/author"Markus S.M."xsd:string
http://purl.uniprot.org/citations/23142046http://purl.uniprot.org/core/author"Kalutkiewicz K.A."xsd:string
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http://purl.uniprot.org/citations/23142046http://purl.uniprot.org/core/pages"2221-2230"xsd:string
http://purl.uniprot.org/citations/23142046http://purl.uniprot.org/core/title"She1-mediated inhibition of dynein motility along astral microtubules promotes polarized spindle movements."xsd:string
http://purl.uniprot.org/citations/23142046http://purl.uniprot.org/core/volume"22"xsd:string
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