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M. Leonard, A. S. Menko; Recruitment of -Catenin, Cortactin and Arp3 to N-Cadherin Junctions as Regulators of Actin Dynamics in Lens Cell Differentiation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1222.
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© ARVO (1962-2015); The Authors (2016-present)
Lens fiber cell differentiation requires both the formation of N-cadherin junctions and the assembly of cortically arranged actin filaments. We now have investigated the in vivo recruitment of molecular regulators of actin dynamics to N-cadherin junctions as the means by which N-cadherin junction formation directs lens fiber cell differentiation and morphogenesis.
Differentiation-specific changes in the recruitment of -catenin, cortactin and Arp3 to N-cadherin junctions was determined by co-immunoprecipitation analysis of microdissected E10 chick embryo lenses. Localization of these proteins to N-cadherin junctions in E10 chick lens sections was determined by confocal microscopy of immunostained sections.
We have previously demonstrated that the assembly of cortically arranged actin filaments is dependent on formation of mature N-cadherin junctions and necessary for lens cell differentiation. Here, by examining the differentiation-state specific recruitment of actin regulators to N-cadherin junctions in vivo, we have revealed the mechanisms by which these junctions regulate assembly of actin filaments for lens cell differentiation. The recruitment of -catenin to cadherin junctions is known to block lamellipodial extension. In the developing lens -catenin became linked to N-cadherin just as the cells establish close cell-cell appositions. Cortactin, an activator of actin filament nucleation, became associated with N-cadherin junctions as lens cells initiated their differentiation, but prior to lens fiber cell morphogenesis. Arp3, a nucleator of actin filament assembly that binds to and is activated by cortactin, was recruited to N-cadherin junctions coincident with rapid cortical actin assembly and fiber cell elongation.
We propose a model whereby recruitment of -catenin to N-cadherin regulates junctional maturation necessary for the initiation of lens fiber cell differentiation, while the N-cadherin/cortactin/Arp3 pathway directs the assembly of actin that extends N-cadherin cell-cell adhesions and generates the forces that drive fiber cell elongation for the establishment of lens cytoarchitecture.
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