DVL1

DVL1, short for Dishevelled segment polarity protein 1, is a cytoplasmic protein encoded by the DVL1 gene in humans. It is a member of the Dishevelled family (DVL1-3) and serves as a central mediator of Wnt signaling. The protein contains three conserved domains—DIX, PDZ, and DEP—that mediate interactions with other signaling proteins and membrane receptors.

DVL1 acts downstream of Wnt receptors, primarily Frizzled, and transduces signals to regulate both canonical Wnt/β-catenin signaling and noncanonical planar cell polarity (PCP) pathways. In canonical signaling, DVL1 helps inhibit the β-catenin destruction complex, allowing β-catenin to accumulate and activate transcription with TCF/LEF in the nucleus. In noncanonical PCP signaling, DVL1 influences cytoskeletal organization and cell polarity via Rho GTPases and downstream effectors, impacting processes such as cell movement and tissue morphogenesis.

Expression of DVL1 is widespread in embryonic and adult tissues, and the protein is essential for normal development. Genetic alterations in DVL1 have been linked to human disease; most notably, DVL1 mutations have been associated with Robinow syndrome, a skeletal dysplasia characterized by facial and limb abnormalities, typically inherited in an autosomal dominant manner. Additional variants in DVL1 or dysregulation of DVL1 function have been explored in cancer and developmental disorders, though roles may be context-dependent.

DVL1 interacts with multiple partners, including Frizzled receptors, AXIN, GSK-3β, and other Dishevelled paralogs, forming a signaling hub that coordinates outputs to various downstream pathways. Ongoing research aims to clarify its precise regulatory mechanisms and tissue-specific roles.