Linked Life Data

21173240

Source:http://linkedlifedata.com/resource/pubmed/id/21173240

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pubmed-article:21173240pubmed:abstractTextDynamic 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 ?4 integrin adhesion receptor is associated with enhanced protrusive activity and regulation of directional cell migration. Among integrin subunits, ?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 ?4 at the leading edge have remained elusive. We generated Abi1 KO mice and found that loss of Abi1 phenocopies KO of ?4. Mice lacking Abi1 or ?4 exhibit midgestational lethality with abnormalities in placental and cardiovascular development. Notably, purified Abi1 protein binds directly to the ?4 cytoplasmic tail and endogenous Abi1 colocalizes with phosphorylated ?4 at the leading edge of spreading cells. Moreover, Abi1-deficient cells expressing ?4 have impaired cell spreading, which is rescued by WT Abi1 but not an Abi1 mutant lacking the ?4-binding site. These data reveal a direct link between the ?4 integrin and actin polymerization and uncover a role for Abi1 in the regulation of morphogenesis in vivo. The Abi1-?4 interaction establishes a mechanistic paradigm for signaling between adhesion events and enhanced actin polymerization at the earliest stages of protrusion.lld:pubmed
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