Dishevelled localization and function are differentially regulated by structurally distinct sterols.

ABSTRACT: The Dishevelled (DVL) family of proteins form supramolecular protein and lipid complexes at the cytoplasmic interface of the plasma membrane to regulate tissue patterning, proliferation, cell polarity, and oncogenic processes through DVL-dependent signaling, such as Wnt/β-catenin. While DVL binding to cholesterol is required for its membrane association, the specific structural requirements and cellular impacts of DVL-sterol association are unclear. We report that intracellular sterols which accumulate within normal and pathological conditions cause aberrant DVL activity. In silico and molecular analyses suggested orientation of the β- and α-sterol face within the DVL-PDZ domain regulates DVL-sterol binding. Intracellular accumulation of naturally occurring sterols impaired DVL2 pla

SUBMITTER: Sengupta S 

PROVIDER: S-EPMC11118412 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature