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Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo

Actin-related protein 2/3 (Arp2/3) complex activation by nucleation promoting factors (NPFs) such as WASP, plays an important role in many actin-mediated cellular processes. In yeast, Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission. Here we used ge...

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Autores principales: Sun, Yidi, Leong, Nicole T, Jiang, Tommy, Tangara, Astou, Darzacq, Xavier, Drubin, David G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559269/
https://www.ncbi.nlm.nih.gov/pubmed/28813247
http://dx.doi.org/10.7554/eLife.29140
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author Sun, Yidi
Leong, Nicole T
Jiang, Tommy
Tangara, Astou
Darzacq, Xavier
Drubin, David G
author_facet Sun, Yidi
Leong, Nicole T
Jiang, Tommy
Tangara, Astou
Darzacq, Xavier
Drubin, David G
author_sort Sun, Yidi
collection PubMed
description Actin-related protein 2/3 (Arp2/3) complex activation by nucleation promoting factors (NPFs) such as WASP, plays an important role in many actin-mediated cellular processes. In yeast, Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission. Here we used genetics and quantitative live-cell imaging to probe the mechanisms that concentrate NPFs at endocytic sites, and to investigate how NPFs regulate actin assembly onset. Our results demonstrate that SH3 (Src homology 3) domain-PRM (proline-rich motif) interactions involving multivalent linker proteins play central roles in concentrating NPFs at endocytic sites. Quantitative imaging suggested that productive actin assembly initiation is tightly coupled to accumulation of threshold levels of WASP and WIP, but not to recruitment kinetics or release of autoinhibition. These studies provide evidence that WASP and WIP play central roles in establishment of a robust multivalent SH3 domain-PRM network in vivo, giving actin assembly onset at endocytic sites a switch-like behavior. DOI: http://dx.doi.org/10.7554/eLife.29140.001
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spelling pubmed-55592692017-08-21 Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo Sun, Yidi Leong, Nicole T Jiang, Tommy Tangara, Astou Darzacq, Xavier Drubin, David G eLife Cell Biology Actin-related protein 2/3 (Arp2/3) complex activation by nucleation promoting factors (NPFs) such as WASP, plays an important role in many actin-mediated cellular processes. In yeast, Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission. Here we used genetics and quantitative live-cell imaging to probe the mechanisms that concentrate NPFs at endocytic sites, and to investigate how NPFs regulate actin assembly onset. Our results demonstrate that SH3 (Src homology 3) domain-PRM (proline-rich motif) interactions involving multivalent linker proteins play central roles in concentrating NPFs at endocytic sites. Quantitative imaging suggested that productive actin assembly initiation is tightly coupled to accumulation of threshold levels of WASP and WIP, but not to recruitment kinetics or release of autoinhibition. These studies provide evidence that WASP and WIP play central roles in establishment of a robust multivalent SH3 domain-PRM network in vivo, giving actin assembly onset at endocytic sites a switch-like behavior. DOI: http://dx.doi.org/10.7554/eLife.29140.001 eLife Sciences Publications, Ltd 2017-08-16 /pmc/articles/PMC5559269/ /pubmed/28813247 http://dx.doi.org/10.7554/eLife.29140 Text en © 2017, Sun et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Sun, Yidi
Leong, Nicole T
Jiang, Tommy
Tangara, Astou
Darzacq, Xavier
Drubin, David G
Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo
title Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo
title_full Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo
title_fullStr Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo
title_full_unstemmed Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo
title_short Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo
title_sort switch-like arp2/3 activation upon wasp and wip recruitment to an apparent threshold level by multivalent linker proteins in vivo
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559269/
https://www.ncbi.nlm.nih.gov/pubmed/28813247
http://dx.doi.org/10.7554/eLife.29140
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