Migfilin and its binding partners: from cell biology to human diseases

Abstract

Links between the plasma membrane and the actin cytoskeleton are essential for maintaining tissue integrity and for controlling cell morphology and behavior. Studies over the past several decades have identified dozens of components of such junctions. One of the most recently identified is migfilin, a widely expressed protein consisting of an N-terminal filamin-binding domain, a central proline-rich domain and three C-terminal LIM domains. Migfilin is recruited to cell-matrix contacts in response to adhesion and colocalizes with β-catenin at cell-cell junctions in epithelial and endothelial cells. Migfilin also travels from the cytoplasm into the nucleus, a process that is regulated by RNA splicing and calcium signaling. Through interactions with multiple binding partners, including Mig-2, filamin and VASP, migfilin links the cell adhesion structures to the actin cytoskeleton. It regulates actin remodeling, cell morphology and motility. In nuclei, migfilin interacts with the cardiac transcriptional factor CSX/NKX2-5 and promotes cardiomyocyte differentiation. It probably functions as a key regulator both at cell adhesion sites and nuclei, coordinating multiple cellular processes, and is implicated in the pathogenesis of several human diseases.

A Suppressive Role of Mitogen Inducible Gene-2 in Mesenchymal Cancer Cell Invasion

“…Sahai and Marshall have shown that the protease-independent amoeboid mode of invasion is enhanced by Rho signaling (1). It is worth noting that Mig-2 interacts with h integrins and promotes focal adhesion formation (20)(21)(22)(23), a process that is known to involve Rho signaling. Thus, it will be interesting to test in future studies whether Mig-2 promotes the protease-independent cancer cell invasion through regulation of Rho signaling.…”

“…Mitogen inducible gene-2 (Mig-2, also known as kindlin-2) is an integrin-binding scaffolding protein that is concentrated at the intracellular face of cell-ECM adhesions, where it links integrins to the actin cytoskeleton (20)(21)(22)(23). Recent studies have shown that Mig-2 is highly expressed in aggressive human TMX2-28 breast cancer cells (24).…”

Migfilin sensitizes cisplatin-induced apoptosis in human glioma cells in vitro

“…The connection between the extracellular matrix (ECM) and adjacent cells plays a significant role in cell fate determination, including differentiation, proliferation, migration and apoptosis [4] . Filamin binding LIM protein 1 (FBLIM1), also known as migfilin, is characterized as a skeleton organization protein that binds to mitogen-inducible gene 2 (Mig-2) at cell-ECM adhesions [5][6][7] .…”

“…The C-terminal region has three sequential LIM domains [8] . In addition, two types of migfilin isoforms have been differentiated as migfilin(s) and FBLP-1 [4,8] . Migfilin(s) is a splicing variant with a proline-rich region deleted, resulting in the loss of the VASP binding site [4,5] .…”

“…In addition, two types of migfilin isoforms have been differentiated as migfilin(s) and FBLP-1 [4,8] . Migfilin(s) is a splicing variant with a proline-rich region deleted, resulting in the loss of the VASP binding site [4,5] . FBLP-1 is missing the third LIM domain, which most likely interferes with the interaction of Mig-2 [4] .…”