Towards Understanding the Angiomotin Membrane Fusion Activity

Date
2021
Language
English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
Abstract

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.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Sears, S., Evans, B., & Kimble-Hill, A. (2021). Towards Understanding the Angiomotin Membrane Fusion Activity. ChemRxiv. https://doi.org/10.26434/chemrxiv-2021-2mtdw
ISSN
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
ChemRxiv
Source
Publisher
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Final published version
Full Text Available at
This item is under embargo {{howLong}}