Asymmetric division triggers cell-specific gene expression through coupled capture and stabilization of a phosphatase

  1. Niels Bradshaw
  2. Richard Losick  Is a corresponding author
  1. Harvard University, United States

Abstract

Formation of a division septum near a randomly chosen pole during sporulation in B. subtilis creates unequal sized daughter cells with dissimilar programs of gene expression. An unanswered question is how polar septation activates a transcription factor (σF) selectively in the small cell. We present evidence that the upstream regulator of σF, the phosphatase SpoIIE, is compartmentalized in the small cell by transfer from the polar septum to the adjacent cell pole where SpoIIE is protected from proteolysis and activated. Polar recognition, protection from proteolysis, and stimulation of phosphatase activity are linked to oligomerization of SpoIIE. This mechanism for initiating cell-specific gene expression is independent of additional sporulation proteins; vegetative cells engineered to divide near a pole sequester SpoIIE and activate σF in small cells. Thus, a simple model explains how SpoIIE responds to a stochastically-generated cue to activate σF at the right time and in the right place.

Article and author information

Author details

  1. Niels Bradshaw

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  2. Richard Losick

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    For correspondence
    losick@mcb.harvard.edu
    Competing interests
    Richard Losick, eLife senior editor.

Reviewing Editor

  1. Michael Laub, Massachusetts Institute of Technology, United States

Version history

  1. Received: April 16, 2015
  2. Accepted: October 13, 2015
  3. Accepted Manuscript published: October 14, 2015 (version 1)
  4. Version of Record published: December 17, 2015 (version 2)
  5. Version of Record updated: April 25, 2017 (version 3)

Copyright

© 2015, Bradshaw & Losick

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Niels Bradshaw
  2. Richard Losick
(2015)
Asymmetric division triggers cell-specific gene expression through coupled capture and stabilization of a phosphatase
eLife 4:e08145.
https://doi.org/10.7554/eLife.08145

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https://doi.org/10.7554/eLife.08145

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    Transcriptomic analyses demonstrated differing time courses of immune responses, with prolonged myeloid cell activity in HD at 1 wk after the first vaccination dose. HD also demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p<0.05). Anti-spike IgG remained elevated above baseline at 6 mo in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development.

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    Funding:

    F30HD102093, F30HL151182, T32HL144909, R01HL138628. This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003.

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