FERM domain-containing protein FRMD5 regulates cell motility via binding to integrin β5 subunit and ROCK1

• FRMD5 interacts with integrin β5 cytoplasmic domain.
• FRMD5 interacts with ROCK1 kinase via its FA domain.
• FRMD5 regulates cellular stress fiber formation by inhibition of ROCK1 kinase activity.
• FRMD5 regulates tumor cell migration by controlling integrin αvβ5-mediated cell–matrix interaction and ROCK1 activation.
• FRMD5 interferes with the interaction of integrin β5 with Kindlin-2 and Talin.

FRMD5 is a novel FERM domain-containing protein depicted in tumor progression. However, the mechanisms underlying FRMD5 inhibition of cell migration is largely unknown. Here, we show that FRMD5 regulates cell migration by interacting with integrin β5 cytoplasmic tail and ROCK1 in human lung cancer cells. FRMD5 promotes cell–matrix adhesion and cell spreading on vitronectin, and thus inhibits cell migration. Furthermore, FRMD5 interacts with ROCK1 and inhibits its activation that leads to the inhibition of myosin light chain phosphorylation and the actin stress fiber formation. Taken together, these findings demonstrate that the putative tumor suppressive protein FRMD5 regulates tumor cell motility via a dual pathway involving FRMD5 binding to integrin β5 tail and to ROCK1.

Structured summary of protein interactionsintegrin B5binds to FRMD5 by pull down (View interaction) integrin B5physically interacts with FRMD5 by pull down (View interaction) FRMD5physically interacts with integrin B5 by anti tag coimmunoprecipitation (View interaction) FRMD5physically interacts with ROCK1 by anti tag coimmunoprecipitation (1, 2) ROCK1physically interacts with FRMD5 by anti bait coip (1, 2) Kindlin-2physically interacts with integrin B5 by anti tag coimmunoprecipitation (View interaction) Talinphysically interacts with integrin B5 by anti tag coimmunoprecipitation (View interaction)