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Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin.

Publication ,  Journal Article
Ring, C; Ginsberg, MH; Haling, J; Pendergast, AM
Published in: Proc Natl Acad Sci U S A
January 4, 2011

Dynamic signals linking the actin cytoskeleton and cell adhesion receptors are essential for morphogenesis during development and normal tissue homeostasis. Abi1 is a central regulator of actin polymerization through interactions with multiple protein complexes. However, the in vivo role of Abi1 remains to be defined. The α4 integrin adhesion receptor is associated with enhanced protrusive activity and regulation of directional cell migration. Among integrin subunits, α4 exhibits unique properties in that it predominantly accumulates at the leading edge of migrating cells; however, the pathways that link the actin-regulatory machinery to α4 at the leading edge have remained elusive. We generated Abi1 KO mice and found that loss of Abi1 phenocopies KO of α4. Mice lacking Abi1 or α4 exhibit midgestational lethality with abnormalities in placental and cardiovascular development. Notably, purified Abi1 protein binds directly to the α4 cytoplasmic tail and endogenous Abi1 colocalizes with phosphorylated α4 at the leading edge of spreading cells. Moreover, Abi1-deficient cells expressing α4 have impaired cell spreading, which is rescued by WT Abi1 but not an Abi1 mutant lacking the α4-binding site. These data reveal a direct link between the α4 integrin and actin polymerization and uncover a role for Abi1 in the regulation of morphogenesis in vivo. The Abi1-α4 interaction establishes a mechanistic paradigm for signaling between adhesion events and enhanced actin polymerization at the earliest stages of protrusion.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 4, 2011

Volume

108

Issue

1

Start / End Page

149 / 154

Location

United States

Related Subject Headings

  • Pregnancy
  • Polymerization
  • Placenta
  • Morphogenesis
  • Microscopy, Fluorescence
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Integrin alpha4
  • Genotype
 

Citation

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ICMJE
MLA
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Ring, C., Ginsberg, M. H., Haling, J., & Pendergast, A. M. (2011). Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin. Proc Natl Acad Sci U S A, 108(1), 149–154. https://doi.org/10.1073/pnas.1012316108
Ring, Colleen, Mark H. Ginsberg, Jacob Haling, and Ann Marie Pendergast. “Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin.Proc Natl Acad Sci U S A 108, no. 1 (January 4, 2011): 149–54. https://doi.org/10.1073/pnas.1012316108.
Ring C, Ginsberg MH, Haling J, Pendergast AM. Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):149–54.
Ring, Colleen, et al. “Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin.Proc Natl Acad Sci U S A, vol. 108, no. 1, Jan. 2011, pp. 149–54. Pubmed, doi:10.1073/pnas.1012316108.
Ring C, Ginsberg MH, Haling J, Pendergast AM. Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):149–154.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 4, 2011

Volume

108

Issue

1

Start / End Page

149 / 154

Location

United States

Related Subject Headings

  • Pregnancy
  • Polymerization
  • Placenta
  • Morphogenesis
  • Microscopy, Fluorescence
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Integrin alpha4
  • Genotype