title: Liprin-α1 and ERC1 control cell edge dynamics by promoting focal adhesion turnover.
abstract: Liprin-α1 and ERC1 are interacting scaffold proteins regulating the motility of normal and tumor cells. They act as part of plasma membrane-associated platforms at the edge of motile cells to promote protrusion by largely unknown mechanisms. Here we identify an amino-terminal region of the liprin-α1 protein (liprin-N) that is sufficient and necessary for the interaction with other liprin-α1 molecules. Similar to liprin-α1 or ERC1 silencing, expression of the liprin-N negatively affects tumor cell motility and extracellular matrix invasion, acting as a dominant negative by interacting with endogenous liprin-α1 and causing the displacement of the endogenous ERC1 protein from the cell edge. Interfering with the localization of ERC1 at the cell edge inhibits the disassembly of focal adhesions, impairing protrusion. Liprin-α1 and ERC1 proteins colocalize with active integrin β1 clusters distinct from those colocalizing with cytoplasmic focal adhesion proteins, and influence the localization of peripheral Rab7-positive endosomes. We propose that liprin-α1 and ERC1 promote protrusion by displacing cytoplasmic adhesion components to favour active integrin internalization into Rab7-positive endosomes.
authors.affiliation: Cell Adhesion Unit, Division of Neuroscience, IRCSS San Raffaele Scientific Institute and San Raffaele University, via Olgettina 58, 20132 Milano, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Astro
authors.affiliation: Cell Adhesion Unit, Division of Neuroscience, IRCSS San Raffaele Scientific Institute and San Raffaele University, via Olgettina 58, 20132 Milano, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Tonoli
authors.affiliation: Cell Adhesion Unit, Division of Neuroscience, IRCSS San Raffaele Scientific Institute and San Raffaele University, via Olgettina 58, 20132 Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Chiaretti
authors.affiliation: Cell Adhesion Unit, Division of Neuroscience, IRCSS San Raffaele Scientific Institute and San Raffaele University, via Olgettina 58, 20132 Milano, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Badanai
authors.affiliation: Cell Adhesion Unit, Division of Neuroscience, IRCSS San Raffaele Scientific Institute and San Raffaele University, via Olgettina 58, 20132 Milano, Italy.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Sala
authors.affiliation: Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden, Germany.
authors.forename: Marino
authors.initials: M
authors.lastname: Zerial
authors.affiliation: Cell Adhesion Unit, Division of Neuroscience, IRCSS San Raffaele Scientific Institute and San Raffaele University, via Olgettina 58, 20132 Milano, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: de Curtis