The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo

网格蛋白适配器AP-1复合物和ARF1调节体内平面细胞极性

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作者:Jose Maria Carvajal-Gonzalez #, Sophie Balmer #, Meg Mendoza, Aurore Dussert, Giovanna Collu, Angel-Carlos Roman, Ursula Weber, Brian Ciruna, Marek Mlodzik

Abstract

A key step in generating planar cell polarity (PCP) is the formation of restricted junctional domains containing Frizzled/Dishevelled/Diego (Fz/Dsh/Dgo) or Van Gogh/Prickle (Vang/Pk) complexes within the same cell, stabilized via Flamingo (Fmi) across cell membranes. Although models have been proposed for how these complexes acquire and maintain their polarized localization, the machinery involved in moving core PCP proteins around cells remains unknown. We describe the AP-1 adaptor complex and Arf1 as major regulators of PCP protein trafficking in vivo. AP-1 and Arf1 disruption affects the accumulation of Fz/Fmi and Vang/Fmi complexes in the proximo-distal axis, producing severe PCP phenotypes. Using novel tools, we demonstrate a direct and specific Arf1 involvement in Fz trafficking in vivo. Moreover, we uncover a conserved Arf1 PCP function in vertebrates. Our data support a model whereby the trafficking machinery plays an important part during PCP establishment, promoting formation of polarized PCP-core complexes in vivo.

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