Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha 4 integrin

作者：Ring Colleen; Gin**erg Mark H; Haling Jacob; Pendergast Ann Marie^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(1): 149-154.

DOI：10.1073/pnas.1012316108

• WAVE complex
• lamellipodia
• chorio-allantoic fusion

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 alpha 4 integrin adhesion receptor is associated with enhanced protrusive activity and regulation of directional cell migration. Among integrin subunits, alpha 4 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 alpha 4 at the leading edge have remained elusive. We generated Abi1 KO mice and found that loss of Abi1 phenocopies KO of alpha 4. Mice lacking Abi1 or alpha 4 exhibit midgestational lethality with abnormalities in placental and cardiovascular development. Notably, purified Abi1 protein binds directly to the alpha 4 cytoplasmic tail and endogenous Abi1 colocalizes with phosphorylated alpha 4 at the leading edge of spreading cells. Moreover, Abi1-deficient cells expressing alpha 4 have impaired cell spreading, which is rescued by WT Abi1 but not an Abi1 mutant lacking the alpha 4-binding site. These data reveal a direct link between the alpha 4 integrin and actin polymerization and uncover a role for Abi1 in the regulation of morphogenesis in vivo. The Abi1-alpha 4 interaction establishes a mechanistic paradigm for signaling between adhesion events and enhanced actin polymerization at the earliest stages of protrusion.

• 出版日期2011-1-4