The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components

GTPase signal transduction pathways control cellular decision making by integrating multiple cellular events into a single signal. The Mitotic Exit Network (MEN), a Ras-like GTPase signaling pathway, integrates spatial and temporal cues to ensure that cytokinesis only occurs after the genome has par...

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Main Authors: Zhou, Xiaoxue, Amon, Angelika B, Campbell, Ian Winsten.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:English
Published: eLife Sciences Publications, Ltd 2020
Online Access:https://hdl.handle.net/1721.1/126157
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author Zhou, Xiaoxue
Amon, Angelika B
Campbell, Ian Winsten.
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Zhou, Xiaoxue
Amon, Angelika B
Campbell, Ian Winsten.
author_sort Zhou, Xiaoxue
collection MIT
description GTPase signal transduction pathways control cellular decision making by integrating multiple cellular events into a single signal. The Mitotic Exit Network (MEN), a Ras-like GTPase signaling pathway, integrates spatial and temporal cues to ensure that cytokinesis only occurs after the genome has partitioned between mother and daughter cells during anaphase. Here we show that signal integration does not occur at a single step of the pathway. Rather, sequential components of the pathway are controlled in series by different signals. The spatial signal, nuclear position, regulates the MEN GTPase Tem1. The temporal signal, commencement of anaphase, is mediated by mitotic cyclin-dependent kinase (CDK) phosphorylation of the GTPase's downstream kinases. We propose that integrating multiple signals through sequential steps in the GTPase pathway represents a generalizable principle in GTPase signaling and explains why intracellular signal transmission is a multi-step process. Serial signal integration rather than signal amplification makes multi-step signal transduction necessary.
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spelling mit-1721.1/1261572022-10-01T22:55:41Z The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components Zhou, Xiaoxue Amon, Angelika B Campbell, Ian Winsten. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT GTPase signal transduction pathways control cellular decision making by integrating multiple cellular events into a single signal. The Mitotic Exit Network (MEN), a Ras-like GTPase signaling pathway, integrates spatial and temporal cues to ensure that cytokinesis only occurs after the genome has partitioned between mother and daughter cells during anaphase. Here we show that signal integration does not occur at a single step of the pathway. Rather, sequential components of the pathway are controlled in series by different signals. The spatial signal, nuclear position, regulates the MEN GTPase Tem1. The temporal signal, commencement of anaphase, is mediated by mitotic cyclin-dependent kinase (CDK) phosphorylation of the GTPase's downstream kinases. We propose that integrating multiple signals through sequential steps in the GTPase pathway represents a generalizable principle in GTPase signaling and explains why intracellular signal transmission is a multi-step process. Serial signal integration rather than signal amplification makes multi-step signal transduction necessary. Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant HD085866) 2020-07-13T17:46:18Z 2020-07-13T17:46:18Z 2019-01 2019-11-26T15:35:57Z Article http://purl.org/eprint/type/JournalArticle 1534-4983 https://hdl.handle.net/1721.1/126157 Campbell, Ian Winsten, Xiaoxue Zhou and Angelika Amon. “The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components.” , vol. 8, 2019, e41139 © 2019 The Author(s) en 10.7554/ELIFE.41139 eLife Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd eLife
spellingShingle Zhou, Xiaoxue
Amon, Angelika B
Campbell, Ian Winsten.
The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components
title The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components
title_full The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components
title_fullStr The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components
title_full_unstemmed The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components
title_short The Mitotic Exit Network integrates temporal and spatial signals by distributing regulation across multiple components
title_sort mitotic exit network integrates temporal and spatial signals by distributing regulation across multiple components
url https://hdl.handle.net/1721.1/126157
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