Filamins regulate cell spreading and initiation of cell migration

Massimiliano Baldassarre, Ziba Razinia, Clara F Burande, Isabelle Lamsoul, Pierre G Lutz, David A Calderwood

Research output: Contribution to journalArticle

68 Citations (Scopus)
5 Downloads (Pure)

Abstract

Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration.Our results establish a role for FLNs in cell migration and spreading and suggest that compensation by other FLNs may mask phenotypes in single knockout or knockdown cells. We propose that interactions between FLNs and transmembrane or signalling proteins, mediated at least in part by immunoglobulin domains 19 to 21 are important for both cell spreading and initiation of migration.

Original languageEnglish
Article numbere7830
JournalPloS ONE
Volume4
Issue number11
DOIs
Publication statusPublished - 2009

Fingerprint

filamin
Filamins
cell movement
Cell Movement
cells
immunoglobulins
microfilament proteins
Immunoglobulins
Periventricular Nodular Heterotopia
Group II Malformations of Cortical Development
Proteolysis
Microfilament Proteins
Aptitude
Locomotion
Masks
proteolysis
Small Interfering RNA
locomotion
Maintenance
Phenotype

Keywords

  • Actins
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Contractile Proteins
  • Filamins
  • Humans
  • Immunoglobulins
  • Jurkat Cells
  • Microfilament Proteins
  • Models, Biological
  • Mutation
  • Phenotype
  • Proteasome Endopeptidase Complex

Cite this

Baldassarre, M., Razinia, Z., Burande, C. F., Lamsoul, I., Lutz, P. G., & Calderwood, D. A. (2009). Filamins regulate cell spreading and initiation of cell migration. PloS ONE, 4(11), [e7830]. https://doi.org/10.1371/journal.pone.0007830

Filamins regulate cell spreading and initiation of cell migration. / Baldassarre, Massimiliano; Razinia, Ziba; Burande, Clara F; Lamsoul, Isabelle; Lutz, Pierre G; Calderwood, David A.

In: PloS ONE, Vol. 4, No. 11, e7830, 2009.

Research output: Contribution to journalArticle

Baldassarre, M, Razinia, Z, Burande, CF, Lamsoul, I, Lutz, PG & Calderwood, DA 2009, 'Filamins regulate cell spreading and initiation of cell migration', PloS ONE, vol. 4, no. 11, e7830. https://doi.org/10.1371/journal.pone.0007830
Baldassarre, Massimiliano ; Razinia, Ziba ; Burande, Clara F ; Lamsoul, Isabelle ; Lutz, Pierre G ; Calderwood, David A. / Filamins regulate cell spreading and initiation of cell migration. In: PloS ONE. 2009 ; Vol. 4, No. 11.
@article{891ea90ed6824ffea5f80772c7433393,
title = "Filamins regulate cell spreading and initiation of cell migration",
abstract = "Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration.Our results establish a role for FLNs in cell migration and spreading and suggest that compensation by other FLNs may mask phenotypes in single knockout or knockdown cells. We propose that interactions between FLNs and transmembrane or signalling proteins, mediated at least in part by immunoglobulin domains 19 to 21 are important for both cell spreading and initiation of migration.",
keywords = "Actins, Animals, Cell Line, Tumor, Cell Movement, Contractile Proteins, Filamins, Humans, Immunoglobulins, Jurkat Cells, Microfilament Proteins, Models, Biological, Mutation, Phenotype, Proteasome Endopeptidase Complex",
author = "Massimiliano Baldassarre and Ziba Razinia and Burande, {Clara F} and Isabelle Lamsoul and Lutz, {Pierre G} and Calderwood, {David A}",
year = "2009",
doi = "10.1371/journal.pone.0007830",
language = "English",
volume = "4",
journal = "PloS ONE",
issn = "1932-6203",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "11",

}

TY - JOUR

T1 - Filamins regulate cell spreading and initiation of cell migration

AU - Baldassarre, Massimiliano

AU - Razinia, Ziba

AU - Burande, Clara F

AU - Lamsoul, Isabelle

AU - Lutz, Pierre G

AU - Calderwood, David A

PY - 2009

Y1 - 2009

N2 - Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration.Our results establish a role for FLNs in cell migration and spreading and suggest that compensation by other FLNs may mask phenotypes in single knockout or knockdown cells. We propose that interactions between FLNs and transmembrane or signalling proteins, mediated at least in part by immunoglobulin domains 19 to 21 are important for both cell spreading and initiation of migration.

AB - Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration.Our results establish a role for FLNs in cell migration and spreading and suggest that compensation by other FLNs may mask phenotypes in single knockout or knockdown cells. We propose that interactions between FLNs and transmembrane or signalling proteins, mediated at least in part by immunoglobulin domains 19 to 21 are important for both cell spreading and initiation of migration.

KW - Actins

KW - Animals

KW - Cell Line, Tumor

KW - Cell Movement

KW - Contractile Proteins

KW - Filamins

KW - Humans

KW - Immunoglobulins

KW - Jurkat Cells

KW - Microfilament Proteins

KW - Models, Biological

KW - Mutation

KW - Phenotype

KW - Proteasome Endopeptidase Complex

U2 - 10.1371/journal.pone.0007830

DO - 10.1371/journal.pone.0007830

M3 - Article

C2 - 19915675

VL - 4

JO - PloS ONE

JF - PloS ONE

SN - 1932-6203

IS - 11

M1 - e7830

ER -