Dimerization and Phosphorylation of Lutheran/basal Cell Adhesion Molecule Are Critical for Its Function in Cell Migration on Laminin

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2019 Aug 16

PMID 31413112

Citations 6

Authors

Anna Guadall

Sylvie Cochet

Olivier Renaud

Yves Colin

Caroline Le Van Kim

Alexandre G de Brevern

Wassim El Nemer

Affiliations

Soon will be listed here.

Abstract

Tumor cell migration depends on the interactions of adhesion proteins with the extracellular matrix. Lutheran/basal cell adhesion molecule (Lu/BCAM) promotes tumor cell migration by binding to laminin α5 chain, a subunit of laminins 511 and 521. Lu/BCAM is a type I transmembrane protein with a cytoplasmic domain of 59 (Lu) or 19 (Lu(v13)) amino acids. Here, using an array of techniques, including site-directed mutagenesis, immunoblotting, FRET, and proximity-ligation assays, we show that both Lu and Lu(v13) form homodimers at the cell surface of epithelial cancer cells. We mapped two small--small motifs in the transmembrane domain as potential sites for monomers docking and identified three cysteines in the cytoplasmic domain as being critical for covalently stabilizing dimers. We further found that Lu dimerization and phosphorylation of its cytoplasmic domain were concomitantly needed to promote cell migration. We conclude that Lu is the critical isoform supporting tumor cell migration on laminin 521 and that the Lu:Lu(v13) ratio at the cell surface may control the balance between cellular firm adhesion and migration.

Citing Articles

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