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Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
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Aurora A Kinase Contributes to a Pole-Based Error Correction Pathway
Anna A Ye1, Jovana Deretic2, Christopher M Hoel3
1Biology Department, University of Massachusetts Amherst, Amherst, MA 01003, USA; Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Current Biology : CB
|July 14, 2015
Summary
Aurora A kinase (AAK) corrects erroneous chromosome attachments near spindle poles by opposing polar ejection forces. This kinase activity ensures proper genome partitioning during cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Accurate chromosome segregation during cell division relies on correct kinetochore-microtubule (MT) attachments.
- Errors in these attachments are common but typically corrected before anaphase, often involving Aurora B kinase (ABK) near spindle poles.
- Polar ejection forces (PEFs) near spindle poles can paradoxically stabilize incorrect attachments, creating a challenge for error correction.
Purpose of the Study:
- To investigate the role of Aurora A kinase (AAK) in correcting erroneous kinetochore-MT attachments.
- To understand how AAK activity influences chromosome alignment and segregation fidelity.
- To elucidate the molecular mechanism by which AAK contributes to error correction near spindle poles.
Main Methods:
- Investigated the effects of AAK inhibition on chromosome alignment and kinetochore-MT attachments.
- Examined AAK's role in phosphorylating kinetochore substrates.
- Analyzed the interaction between AAK, PEFs, and the Ndc80 complex.
Main Results:
- AAK inhibition leads to chromosome misalignment and increased erroneous kinetochore-MT attachments.
- AAK activity phosphorylates kinetochore substrates near spindle poles, counteracting PEF-mediated stabilization.
- AAK directly phosphorylates the Ndc80/Hec1 complex, reducing its MT binding affinity.
Conclusions:
- AAK plays a crucial role in correcting mal-oriented kinetochore-MT attachments, particularly near spindle poles.
- An AAK activity gradient contributes to the fidelity of chromosome segregation by opposing PEF effects.
- AAK's phosphorylation of Ndc80/Hec1 is a key mechanism for resolving improper attachments.
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