Browsing by Subject "phosphatidylinositol"

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    Towards Understanding the Angiomotin Membrane Fusion Activity
    (2021) Sears, Seth; Evans, Brenner; Kimble-Hill, Ann C.; Biochemistry and Molecular Biology, School of Medicine
    Angiomotins (Amot) are a family of adaptor proteins that regulate cellular differentiation and proliferation signaling. These cellular events are linked to the initiation of invasive ductal carcinoma, the most common form of breast cancer. Their characteristic coiled-coil homology (ACCH) domain selectively binds phosphatidylinositol lipids (PI), leading to membrane deformation and fusion events necessary for the trafficking polarity proteins to and from the apical membrane. We have previously shown that the ACCH domain has the ability to reorganize and homogenize the PI-enriched microdomains in membranes. However, the connection between the membrane fusion activity and the homogenization of PI has not been well described. In this study, we use small angle x-ray scattering (SAXS) to demonstrate the lipid reorganization function and fluorescence resonance energy transfer (FRET) to characterize the vesicle fusion activity. As a result, we found 6 mutations in the ACCH domain that caused a loss of fusion activity. Furthermore, these mutations also have lost lipid reorganization activity. The results presented provide insight into the role of the Amot ACCH domain residues in driving membrane fusion events involved in targeting and recycling cellular polarity proteins to maintain normal cellular phenotypes.