Cortical dynein pulling mechanism is regulated by differentially targeted attachment molecule Num1

@article{Omer2018CorticalDP,
  title={Cortical dynein pulling mechanism is regulated by differentially targeted attachment molecule Num1},
  author={Safia Omer and Samuel R Greenberg and Wei-Lih Lee},
  journal={eLife},
  year={2018},
  volume={7}
}
Cortical dynein generates pulling forces via microtubule (MT) end capture-shrinkage and lateral MT sliding mechanisms. In Saccharomyces cerevisiae, the dynein attachment molecule Num1 interacts with endoplasmic reticulum (ER) and mitochondria to facilitate spindle positioning across the mother-bud neck, but direct evidence for how these cortical contacts regulate dynein-dependent pulling forces is lacking. We show that loss of Scs2/Scs22, ER tethering proteins, resulted in defective Num1… 
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25 Citations

Overexpression of Mdm36 reveals Num1 foci that mediate dynein-dependent microtubule sliding in budding yeast

It is proposed that formation of small ensembles of attachment molecules is sufficient for dynein anchorage and cortical generation of large spindle-pulling force.

Overexpression of Mdm36 reveals Num1 foci that mediate dynein-dependent microtubule sliding in budding yeast

Using Mdm36 as a tool to cluster Num1 at the cell cortex reveals that there are two distinct populations of Num1, each mediating its role in spindle positioning and mitochondrial tethering, respectively.

Dynein collective behavior in mitotic nuclear positioning of Saccharomyces cerevisiae

A computational model of nuclear mobility in S. cerevisiae is used and the apparent random-walk mobility of spindle pole bodies measured by quantifying fluorescence microscopy time-series is reconciled to predict a functional role for dynein clustering in nuclear positioning.

Insights into LIS1 function in cargo-adapter-mediated dynein activation in vivo

The role of Lissencephaly 1 (LIS1) is revealed and a novel mechanism of LIS1 action involving a switch of dynein from an auto-inhibited state to an active state is discovered.

Systematic analysis of microtubule plus-end networks defines EB-cargo complexes critical for mitosis in budding yeast

This study demonstrates that the budding yeast EB protein Bim1 executes its key mitotic functions as part of two cargo complexes-Bim1-Kar9 in the cytoplasm and Bim2-Cik1- Kar3 in the nucleus, and reveals compensatory mechanisms that allow cells to proliferate in the absence of BIM1.

The cortical force-generating machinery: how cortical spindle-pulling forces are generated.

Temporal control of Num1 contact site formation reveals a relationship between mitochondrial division and mitochondria-plasma membrane tethering

It is found that mitochondria-PM tethering alone is not sufficient to rescue mitochondrial division and that a specific feature of Num1-mediated tethering is required, demonstrating the utility of systems that regulate contact site formation and depletion in studying the biological functions of membrane contact sites.

Num1 versus NuMA: insights from two functionally homologous proteins

Evidence supporting that Num1 in fungi is a functional homolog of NuMA due to their similarity in domain organization and role in the generation of cortical pulling forces is discussed.

Developmental regulation of an organelle tether coordinates mitochondrial remodeling in meiosis

This study defines a key mechanism that coordinates mitochondrial morphogenesis with the landmark events of meiosis and demonstrates that cells can developmentally regulate tethering to induce organelle remodeling.

Nuclear positioning during development: Pushing, pulling and flowing.

118 References

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Dynein Tethers and Stabilizes Dynamic Microtubule Plus Ends

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