Functional Hierarchy of Redundant Actin Assembly Factors Revealed by Fine-Grained Registration of Intrinsic Image Fluctuations

Kwonmoo Lee, Hunter L. Elliott, Youbean Oak, Chih Te Zee, Alex Groisman, Jessica D. Tytell, Gaudenz Danuser

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Summary Highly redundant pathways often contain components whose functions are difficult to decipher from the responses induced by genetic or molecular perturbations. Here, we present a statistical approach that samples and registers events observed in images of intrinsic fluctuations in unperturbed cells to establish the functional hierarchy of events in systems with redundant pathways. We apply this approach to study the recruitment of actin assembly factors involved in the protrusion of the cell membrane. We find that the formin mDia1, along with nascent adhesion components, is recruited to the leading edge of the cell before protrusion onset, initiating linear growth of the lamellipodial network. Recruitment of Arp2/3, VASP, cofilin, and the formin mDia2 then promotes sustained exponential growth of the network. Experiments changing membrane tension suggest that Arp2/3 recruitment is mechano-responsive. These results indicate that cells adjust the overlapping contributions of multiple factors to actin filament assembly during protrusion on a 10-s timescale and in response to mechanical cues.

Original languageEnglish (US)
Article number7
Pages (from-to)37-50
Number of pages14
JournalCell Systems
Volume1
Issue number1
DOIs
StatePublished - Jul 29 2015

Fingerprint

Actins
Cell Surface Extensions
Actin Depolymerizing Factors
Growth
Actin Cytoskeleton
Cues
Molecular Biology
Membranes

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Pathology and Forensic Medicine

Cite this

Functional Hierarchy of Redundant Actin Assembly Factors Revealed by Fine-Grained Registration of Intrinsic Image Fluctuations. / Lee, Kwonmoo; Elliott, Hunter L.; Oak, Youbean; Zee, Chih Te; Groisman, Alex; Tytell, Jessica D.; Danuser, Gaudenz.

In: Cell Systems, Vol. 1, No. 1, 7, 29.07.2015, p. 37-50.

Research output: Contribution to journalArticle

Lee, Kwonmoo ; Elliott, Hunter L. ; Oak, Youbean ; Zee, Chih Te ; Groisman, Alex ; Tytell, Jessica D. ; Danuser, Gaudenz. / Functional Hierarchy of Redundant Actin Assembly Factors Revealed by Fine-Grained Registration of Intrinsic Image Fluctuations. In: Cell Systems. 2015 ; Vol. 1, No. 1. pp. 37-50.
@article{e83273121bbd4075a6c9e8188ce144c0,
title = "Functional Hierarchy of Redundant Actin Assembly Factors Revealed by Fine-Grained Registration of Intrinsic Image Fluctuations",
abstract = "Summary Highly redundant pathways often contain components whose functions are difficult to decipher from the responses induced by genetic or molecular perturbations. Here, we present a statistical approach that samples and registers events observed in images of intrinsic fluctuations in unperturbed cells to establish the functional hierarchy of events in systems with redundant pathways. We apply this approach to study the recruitment of actin assembly factors involved in the protrusion of the cell membrane. We find that the formin mDia1, along with nascent adhesion components, is recruited to the leading edge of the cell before protrusion onset, initiating linear growth of the lamellipodial network. Recruitment of Arp2/3, VASP, cofilin, and the formin mDia2 then promotes sustained exponential growth of the network. Experiments changing membrane tension suggest that Arp2/3 recruitment is mechano-responsive. These results indicate that cells adjust the overlapping contributions of multiple factors to actin filament assembly during protrusion on a 10-s timescale and in response to mechanical cues.",
author = "Kwonmoo Lee and Elliott, {Hunter L.} and Youbean Oak and Zee, {Chih Te} and Alex Groisman and Tytell, {Jessica D.} and Gaudenz Danuser",
year = "2015",
month = "7",
day = "29",
doi = "10.1016/j.cels.2015.07.001",
language = "English (US)",
volume = "1",
pages = "37--50",
journal = "Cell Systems",
issn = "2405-4712",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Functional Hierarchy of Redundant Actin Assembly Factors Revealed by Fine-Grained Registration of Intrinsic Image Fluctuations

AU - Lee, Kwonmoo

AU - Elliott, Hunter L.

AU - Oak, Youbean

AU - Zee, Chih Te

AU - Groisman, Alex

AU - Tytell, Jessica D.

AU - Danuser, Gaudenz

PY - 2015/7/29

Y1 - 2015/7/29

N2 - Summary Highly redundant pathways often contain components whose functions are difficult to decipher from the responses induced by genetic or molecular perturbations. Here, we present a statistical approach that samples and registers events observed in images of intrinsic fluctuations in unperturbed cells to establish the functional hierarchy of events in systems with redundant pathways. We apply this approach to study the recruitment of actin assembly factors involved in the protrusion of the cell membrane. We find that the formin mDia1, along with nascent adhesion components, is recruited to the leading edge of the cell before protrusion onset, initiating linear growth of the lamellipodial network. Recruitment of Arp2/3, VASP, cofilin, and the formin mDia2 then promotes sustained exponential growth of the network. Experiments changing membrane tension suggest that Arp2/3 recruitment is mechano-responsive. These results indicate that cells adjust the overlapping contributions of multiple factors to actin filament assembly during protrusion on a 10-s timescale and in response to mechanical cues.

AB - Summary Highly redundant pathways often contain components whose functions are difficult to decipher from the responses induced by genetic or molecular perturbations. Here, we present a statistical approach that samples and registers events observed in images of intrinsic fluctuations in unperturbed cells to establish the functional hierarchy of events in systems with redundant pathways. We apply this approach to study the recruitment of actin assembly factors involved in the protrusion of the cell membrane. We find that the formin mDia1, along with nascent adhesion components, is recruited to the leading edge of the cell before protrusion onset, initiating linear growth of the lamellipodial network. Recruitment of Arp2/3, VASP, cofilin, and the formin mDia2 then promotes sustained exponential growth of the network. Experiments changing membrane tension suggest that Arp2/3 recruitment is mechano-responsive. These results indicate that cells adjust the overlapping contributions of multiple factors to actin filament assembly during protrusion on a 10-s timescale and in response to mechanical cues.

UR - http://www.scopus.com/inward/record.url?scp=84938359661&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938359661&partnerID=8YFLogxK

U2 - 10.1016/j.cels.2015.07.001

DO - 10.1016/j.cels.2015.07.001

M3 - Article

VL - 1

SP - 37

EP - 50

JO - Cell Systems

JF - Cell Systems

SN - 2405-4712

IS - 1

M1 - 7

ER -