Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity

Thomas J. Lampert, Nadine Kamprad, Marc Edwards, Jane Borleis, Ayende J. Watson, Marco Tarantola, Peter N Devreotes

Research output: Contribution to journalArticle

Abstract

The model organism Dictyostelium discoideum has greatly facilitated our understanding of the signal transduction and cytoskeletal pathways that govern cell motility. Cell–substrate adhesion is downstream of many migratory and chemotaxis signaling events. Dictyostelium cells lacking the tumor suppressor PTEN show strongly impaired migratory activity and adhere strongly to their substrates. We reasoned that other regulators of migration could be obtained through a screen for overly adhesive mutants. A screen of restriction enzyme-mediated integration mutagenized cells yielded numerous mutants with the desired phenotypes, and the insertion sites in 18 of the strains were mapped. These regulators of adhesion and motility mutants have increased adhesion and decreased motility. Characterization of seven strains demonstrated decreased directed migration, flatness, increased filamentous actin-based protrusions, and increased signal transduction network activity. Many of the genes share homology to human genes and demonstrate the diverse array of cellular networks that function in adhesion and migration.

Original languageEnglish (US)
Pages (from-to)E7727-E7736
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number37
DOIs
StatePublished - Sep 12 2017

Fingerprint

Dictyostelium
Cell Adhesion
Signal Transduction
Chemotaxis
Adhesives
Genes
Cell Movement
Actins
Phenotype
Enzymes
Neoplasms

Keywords

  • Cell adhesion
  • Cell migration
  • Chemotaxis
  • Dictyostelium
  • PTEN

ASJC Scopus subject areas

  • General

Cite this

Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity. / Lampert, Thomas J.; Kamprad, Nadine; Edwards, Marc; Borleis, Jane; Watson, Ayende J.; Tarantola, Marco; Devreotes, Peter N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 37, 12.09.2017, p. E7727-E7736.

Research output: Contribution to journalArticle

Lampert, Thomas J. ; Kamprad, Nadine ; Edwards, Marc ; Borleis, Jane ; Watson, Ayende J. ; Tarantola, Marco ; Devreotes, Peter N. / Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 37. pp. E7727-E7736.
@article{17ebbb5451ae4bdc83de033ad9b129dd,
title = "Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity",
abstract = "The model organism Dictyostelium discoideum has greatly facilitated our understanding of the signal transduction and cytoskeletal pathways that govern cell motility. Cell–substrate adhesion is downstream of many migratory and chemotaxis signaling events. Dictyostelium cells lacking the tumor suppressor PTEN show strongly impaired migratory activity and adhere strongly to their substrates. We reasoned that other regulators of migration could be obtained through a screen for overly adhesive mutants. A screen of restriction enzyme-mediated integration mutagenized cells yielded numerous mutants with the desired phenotypes, and the insertion sites in 18 of the strains were mapped. These regulators of adhesion and motility mutants have increased adhesion and decreased motility. Characterization of seven strains demonstrated decreased directed migration, flatness, increased filamentous actin-based protrusions, and increased signal transduction network activity. Many of the genes share homology to human genes and demonstrate the diverse array of cellular networks that function in adhesion and migration.",
keywords = "Cell adhesion, Cell migration, Chemotaxis, Dictyostelium, PTEN",
author = "Lampert, {Thomas J.} and Nadine Kamprad and Marc Edwards and Jane Borleis and Watson, {Ayende J.} and Marco Tarantola and Devreotes, {Peter N}",
year = "2017",
month = "9",
day = "12",
doi = "10.1073/pnas.1616600114",
language = "English (US)",
volume = "114",
pages = "E7727--E7736",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "37",

}

TY - JOUR

T1 - Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity

AU - Lampert, Thomas J.

AU - Kamprad, Nadine

AU - Edwards, Marc

AU - Borleis, Jane

AU - Watson, Ayende J.

AU - Tarantola, Marco

AU - Devreotes, Peter N

PY - 2017/9/12

Y1 - 2017/9/12

N2 - The model organism Dictyostelium discoideum has greatly facilitated our understanding of the signal transduction and cytoskeletal pathways that govern cell motility. Cell–substrate adhesion is downstream of many migratory and chemotaxis signaling events. Dictyostelium cells lacking the tumor suppressor PTEN show strongly impaired migratory activity and adhere strongly to their substrates. We reasoned that other regulators of migration could be obtained through a screen for overly adhesive mutants. A screen of restriction enzyme-mediated integration mutagenized cells yielded numerous mutants with the desired phenotypes, and the insertion sites in 18 of the strains were mapped. These regulators of adhesion and motility mutants have increased adhesion and decreased motility. Characterization of seven strains demonstrated decreased directed migration, flatness, increased filamentous actin-based protrusions, and increased signal transduction network activity. Many of the genes share homology to human genes and demonstrate the diverse array of cellular networks that function in adhesion and migration.

AB - The model organism Dictyostelium discoideum has greatly facilitated our understanding of the signal transduction and cytoskeletal pathways that govern cell motility. Cell–substrate adhesion is downstream of many migratory and chemotaxis signaling events. Dictyostelium cells lacking the tumor suppressor PTEN show strongly impaired migratory activity and adhere strongly to their substrates. We reasoned that other regulators of migration could be obtained through a screen for overly adhesive mutants. A screen of restriction enzyme-mediated integration mutagenized cells yielded numerous mutants with the desired phenotypes, and the insertion sites in 18 of the strains were mapped. These regulators of adhesion and motility mutants have increased adhesion and decreased motility. Characterization of seven strains demonstrated decreased directed migration, flatness, increased filamentous actin-based protrusions, and increased signal transduction network activity. Many of the genes share homology to human genes and demonstrate the diverse array of cellular networks that function in adhesion and migration.

KW - Cell adhesion

KW - Cell migration

KW - Chemotaxis

KW - Dictyostelium

KW - PTEN

UR - http://www.scopus.com/inward/record.url?scp=85029501236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029501236&partnerID=8YFLogxK

U2 - 10.1073/pnas.1616600114

DO - 10.1073/pnas.1616600114

M3 - Article

C2 - 28847951

AN - SCOPUS:85029501236

VL - 114

SP - E7727-E7736

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 37

ER -