The type III TGFβ receptor regulates filopodia formation via a Cdc42-mediated IRSp53-N-WASP interaction in epithelial cells

Sun Young Oh, Erik H. Knelson, Gerard C. Blobe, Karthikeyan Mythreye

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Cell adhesion and migration are tightly controlled by regulated changes in the actin cytoskeleton. Previously we reported that the TGFβ (transforming growth factor β) superfamily co-receptor, TβRIII (type III TGFβ receptor; also known as betaglycan), regulates cell adhesion, migration and invasion, and suppresses cancer progression, in part, through activation of the smallGTPase Cdc42 (cell division cycle 42), and Cdc42-dependent alterations to the actin cytoskeleton. In the present study we demonstrate that TβRIII specifically promotes filopodial formation and extension in MCF10A and HMEC (human mammary epithelial cell) mammary epithelial cells. Mechanistically, cell-surface TβRIII and Cdc42 co-localize to filopodial structures and co-complex in a β-Arrestin2-dependent, and a TβRI/TβRII- independent manner. The β-Arrestin2-mediated interaction between TβRIII and Cdc42 increases complex formation between theCdc42 effectors IRSp53 with N-WASP (neuronal Wiskott-Aldrich syndrome protein) to increase filopodial formation. We demonstrate a function link between filopodial structures and epithelial cell adhesion as regulated by the TβRIII-Cdc42 interaction. The present studies identify TβRIII as a novel regulator of IRSp53/N-WASP via Cdc42 to regulate filopodial formation and cell adhesion.

Original languageEnglish (US)
Pages (from-to)79-89
Number of pages11
JournalBiochemical Journal
Volume454
Issue number1
DOIs
StatePublished - Aug 15 2013
Externally publishedYes

Fingerprint

Neuronal Wiskott-Aldrich Syndrome Protein
Pseudopodia
Growth Factor Receptors
Cell adhesion
Transforming Growth Factors
Cell Cycle
Epithelial Cells
Cell Adhesion
Actins
Actin Cytoskeleton
Cell Movement
Breast
Chemical activation
Cells

Keywords

  • β-Arrestin2
  • Cell division cycle 42 (cdc42)
  • Filopodium
  • Irsp53
  • Type iii transforming growth factor β receptor (tβriii)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

The type III TGFβ receptor regulates filopodia formation via a Cdc42-mediated IRSp53-N-WASP interaction in epithelial cells. / Oh, Sun Young; Knelson, Erik H.; Blobe, Gerard C.; Mythreye, Karthikeyan.

In: Biochemical Journal, Vol. 454, No. 1, 15.08.2013, p. 79-89.

Research output: Contribution to journalArticle

Oh, Sun Young ; Knelson, Erik H. ; Blobe, Gerard C. ; Mythreye, Karthikeyan. / The type III TGFβ receptor regulates filopodia formation via a Cdc42-mediated IRSp53-N-WASP interaction in epithelial cells. In: Biochemical Journal. 2013 ; Vol. 454, No. 1. pp. 79-89.
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