Angiomotin Regulates Endothelial Cell-Cell Junctions and Cell Motility

Abstract

We have previously identified angiomotin by its ability to bind to and mediate the anti-angiogenic properties of angiostatin. In vivo and in vitro data indicate an essential role of angiomotin in endothelial cell motility. Here we show that angiostatin binds angiomotin on the cell surface and provide evidence for a transmembrane model for the topology of both p80 and p130 angiomotin isoforms. Immunofluorescence analysis shows that angiomotin co-localized with ZO-1 in cell-cell contacts in endothelial cells in vitro and in angiogenic blood vessels of the postnatal mouse retina in vivo. Transfection of p80 as well as p130 angiomotin in Chinese hamster ovary cells resulted in junctional localization of both isoforms. Furthermore, p130 angiomotin could recruit ZO-1 to actin stress fibers. The p130 but not p80 isoform could be coprecipitated with MAGI-1b, a component of endothelial tight junctions. Paracellular permeability, as measured by diffusion of fluorescein isothiocyanate-dextran, was reduced by p80 and p130 angiomotin expression with 70 and 88%, respectively, compared with control. Angiostatin did not have any effect on cell permeability but inhibited the migration of angiomotin-expressing cells in the Boyden chamber assay. We conclude that angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions.

Rab13-dependent Trafficking of RhoA Is Required for Directional Migration and Angiogenesis

“…Similarly, the role of Amot in Rab13-dependent trafficking of Syx and RhoA may explain how Amot regulates both cell migration and cell junctions (58). The involvement of Patj/Mupp1 and Amot in the regulation of directional cell migration conveys a common theme whereby junctional proteins are required also for cell migration, a seemingly counterintuitive notion.…”

Soluble Melanoma Cell Adhesion Molecule (sMCAM/sCD146) Promotes Angiogenic Effects on Endothelial Progenitor Cells through Angiomotin

“…Initially, angiomotin has been identified in a yeast two-hybrid screen by its ability to bind angiostatin, a circulating inhibitor of blood vessels formation (9). Angiomotin is a membrane-associated protein expressed on human endothelium that promotes angiogenesis by controlling directional migration (11,12). Accordingly, therapeutic antibodies targeting angiomotin have been shown to inhibit angiogenesis both in vitro and in vivo (13).…”

Opposing roles of angiomotin-like-1 and zona occludens-2 on pro-apoptotic function of YAP

“…In addition, Amot was shown to be a part of the actin cytoskeleton and cell-to-cell junction complexes. Amot is a member of a family of proteins composed of Amot and two paralogs, angiomotin-like-1 (AmotL1) and angiomotin-like-2 (AmotL2) (Nishimura et al, 2002;Bratt et al, 2005).…”