Cell cycle regulation of ER membrane biogenesis protects against chromosome missegregation

Holly Merta1, Jake W Carrasquillo Rodríguez1, Maya I Anjur-Dietrich2

  • 1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.

Developmental Cell
|December 1, 2021
PubMed

Insights

Accurate cell division requires controlling endoplasmic reticulum (ER) size. Proper ER membrane production prevents errors in chromosome segregation, reducing micronuclei formation and supporting mitotic fidelity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Endoplasmic reticulum (ER) reorganization is crucial for accurate chromosome segregation during mitosis.
  • Failure to manage ER structure can lead to mitotic errors and aneuploidy.

Purpose of the Study:

  • To investigate the role of cell cycle-regulated ER membrane production in maintaining mitotic fidelity.
  • To elucidate the molecular mechanisms controlling ER biogenesis and its impact on chromosome segregation.

Main Methods:

  • Utilized human cell lines.
  • Investigated protein phosphatase CTDNEP1, mTOR kinase, and lipin 1 pathways.
  • Analyzed ER membrane biogenesis and its effect on cytoplasmic viscosity and chromosome movement during mitosis.

Main Results:

  • Cell cycle-regulated ER membrane production is essential for accurate chromosome segregation.
  • Excess ER membranes increase cytoplasmic viscosity, hindering error correction and promoting micronuclei formation.
  • CTDNEP1 counteracts mTOR to limit interphase ER membrane synthesis, thereby preventing mitotic errors.

Conclusions:

  • Regulation of ER size is a key determinant of mitotic cell biophysics and fidelity.
  • Dysregulated lipid metabolism and ER biogenesis contribute to aneuploidy, potentially in cancer cells.

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