TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, and CENP-E recruitment

Miroslav P Milev1, Benedeta Hasaj1, Djenann Saint-Dic1

  • 1Department of Biology, Concordia University, Montreal, Quebec H4B 1R6, Canada.

Insights

The protein TRAMM is crucial for mitosis, ensuring stable kinetochore-microtubule attachments. Its phosphorylation cycle regulates CENP-E recruitment, vital for chromosome congression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Chromosome congression relies on stable microtubule-kinetochore attachments.
  • The assembly mechanism of kinetochores, essential for this process, remains largely unknown.

Purpose of the Study:

  • To investigate the role of the protein TRAMM (formerly TrappC12) in mitosis.
  • To elucidate TRAMM's function in kinetochore assembly and chromosome congression.

Main Methods:

  • Depletion of TRAMM using specific techniques.
  • Analysis of chromosome congression and cell cycle progression.
  • Immunofluorescence to assess kinetochore protein localization.
  • Co-immunoprecipitation to study protein interactions.
  • Phosphorylation analysis of TRAMM during mitosis.

Main Results:

  • TRAMM depletion leads to noncongressed chromosomes and mitotic arrest.
  • TRAMM associates with chromosomes and affects kinetochore protein localization, notably CENP-E.
  • TRAMM interacts with CENP-E and is required for its kinetochore recruitment.
  • TRAMM phosphorylation/dephosphorylation cycle correlates with CENP-E binding.
  • A phosphomimetic TRAMM mutant enhances CENP-E recruitment to kinetochores.

Conclusions:

  • TRAMM plays a critical role in mitosis, acting as a novel regulator of kinetochore stability.
  • TRAMM's phosphorylation-dependent interaction with CENP-E is essential for proper chromosome congression.
  • This study reveals a moonlighting function for TRAMM in ensuring accurate cell division.

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