mDia1

mDia1, or diaphanous-related formin 1, is a mammalian actin-regulating protein belonging to the formin family. It is encoded by the DIAPH1 gene and is a key effector in Rho GTPase signaling that promotes actin filament nucleation and elongated polymerization. It contributes to the organization of linear actin cables that support cell shape and migration.

Structurally, mDia1 contains an N-terminal GTPase-binding domain (GBD), followed by an autoregulatory diaphanous inhibitory domain (DID), a coiled-coil dimerization region, and a diaphanous autoregulatory domain (DAD) at the C-terminus. Downstream of the DAD lie the formin homology 1 (FH1) and formin homology 2 (FH2) domains, with FH1 rich in profilin-binding motifs that deliver profilin–actin to the FH2 for filament elongation. Autoinhibition arises from DID–DAD interaction; binding of RhoA–GTP to the GBD relieves this inhibition and activates actin assembly.

During activation, the FH2 domain remains associated with the growing barbed end of actin filaments, enabling processive elongation, while FH1 recruits profilin–actin to accelerate monomer addition. mDia1 preferentially promotes linear, unbranched filaments and plays a role in stress fiber formation, focal adhesion dynamics, and filopodium formation. It also participates in crosstalk with microtubules and contributes to cell polarity and cytokinesis.

mDia1 localizes to sites of active cytoskeletal remodeling, including the leading edge of migrating cells and the cleavage furrow during division. Through its regulatory interactions, it integrates signals from Rho GTPases with cytoskeletal remodeling programs that govern movement, shape, and division.

Abnormal DIAPH1/mDia1 activity has been linked to human disease in studies of cytoskeletal regulation, and ongoing research aims to clarify its precise roles in development, physiology, and pathology.