title: Liprin-α1, ERC1 and LL5 define polarized and dynamic structures that are implicated in cell migration.
abstract: Cell migration during development and metastatic invasion requires the coordination of actin and adhesion dynamics to promote protrusive activity at the front of the cell. The knowledge of the molecular mechanisms required to achieve such coordination is fragmentary. Here, we identify a new functional complex that drives cell motility. ERC1a (an isoform of ERC1) and the LL5 proteins LL5α and LL5β (encoded by PHLDB1 and PHLDB2, respectively) are required, together with liprin-α1, for effective migration and tumor cell invasion, and do so by stabilizing the protrusive activity at the cell front. Depletion of either protein negatively affects invasion, migration on extracellular matrix, lamellipodial persistence and the internalization of active integrin β1 receptors needed for adhesion turnover at the front of the cell. Liprin-α1, ERC1a and LL5 also define new highly polarized and dynamic cytoplasmic structures uniquely localized near the protruding cell edge. Our results indicate that the functional complex and the associated structures described here represent an important mechanism to drive tumor cell migration.
authors: Cell Adhesion Unit, San Raffaele Scientific Institute, 20132 Milano, Italy.
authors: Veronica
authors: V
authors: Astro
authors: Cell Adhesion Unit, San Raffaele Scientific Institute, 20132 Milano, Italy.
authors: Sara
authors: S
authors: Chiaretti
authors: Cell Adhesion Unit, San Raffaele Scientific Institute, 20132 Milano, Italy.
authors: Elisa
authors: E
authors: Magistrati
authors: Duke-NUS Graduate Medical School Singapore, 169857 Singapore.
authors: Marc
authors: M
authors: Fivaz
authors: Cell Adhesion Unit, San Raffaele Scientific Institute, 20132 Milano, Italy San Raffaele University, 20132 Milano, Italy decurtis.ivan@hsr.it.
authors: Ivan
authors: I
authors: de Curtis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C468925:ERC1 protein, human; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C487973:PHLDB1 protein, human; C471180:PHLDB2 protein, human
keywords: Integrin; Invasion; Lamellipodia; Migration