mDia2

Mdia2, or mammalian diaphanous-related formin 2, is a member of the formin family of actin-nucleating proteins. In humans it is encoded by the DIAPH3 gene. As with other formins, mDia2 plays a central role in organizing the actin cytoskeleton and influencing cell shape, polarity, and movement.

The protein architecture comprises an N-terminal GTPase-binding domain (GBD) followed by a diaphanous inhibitory domain (DID), a dimerization domain (DD), and a coiled-coil region, leading to the C-terminal formin homology domains FH1 and FH2, and a diaphanous autoinhibitory domain (DAD). In its inactive state, the DID–DAD interaction keeps mDia2 autoinhibited. Binding of Rho family GTPases (such as RhoA, Rif, and Cdc42) to the GBD relieves this autoinhibition, enabling actin nucleation and elongation.

Functionally, mDia2 promotes the formation of unbranched actin filaments through the FH2 domain and supplies profilin-bound actin monomers via the proline-rich FH1 region. It participates in the generation of actin-based structures such as filopodia and lamellipodia, and it supports processes like polarized cell migration, cytokinesis, and vesicle trafficking. The protein can also interact with microtubules, contributing to coordinated cytoskeletal remodeling.

Regulation of mDia2 activity is achieved by small GTPases, phosphorylation events, and interactions with other cytoskeletal and signaling proteins, which influence its localization and functional output. Expression is widespread, with notable activity in cells undergoing dynamic cytoskeletal rearrangements, including developing neurons and migrating cells.