Transfer of the Septin Ring to Cytokinetic Remnants in ER Stress Directs Age-Sensitive Cell-Cycle Re-entry

Dev Cell. 2019 Oct 21;51(2):173-191.e5. doi: 10.1016/j.devcel.2019.08.017. Epub 2019 Sep 26.

Abstract

During cell division, the inheritance of a functional endoplasmic reticulum (ER) is ensured by the endoplasmic reticulum stress surveillance (ERSU) pathway. Activation of ERSU causes the septin ring to mislocalize, which blocks ER inheritance and cytokinesis. Here, we uncover that the septin ring in fact translocates to previously utilized cell division sites called cytokinetic remnants (CRMs). This unconventional translocation requires Nba1, a negative polarity regulator that normally prevents repolarization and re-budding at CRMs. Furthermore, septin ring translocation relies on the recruitment and activation of a key ERSU component Slt2 by Bem1, without activating Cdc42. Failure to transfer all septin subunits to CRMs delays the cell's ability to re-enter the cell cycle when ER homeostasis is restored and hinders cell growth after ER stress recovery. Thus, these deliberate but unprecedented rearrangements of cell polarity factors during ER stress safeguard cell survival and the timely cell-cycle re-entry upon ER stress recovery.

Keywords: Cdc42; ER inheritance block; ER stress; ERSU; Slt2 MAP Kinase; aging; cell polarity; cell-cycle; cytokinetic remnants; septin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Cycle / physiology*
  • Cell Division / physiology
  • Cell Polarity / physiology*
  • Cytokinesis / physiology
  • Cytoskeleton / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum Stress / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Septins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Mitogen-Activated Protein Kinases
  • Septins