Structural and Functional Determinants of AC8 Trafficking, Targeting and Responsiveness in Lipid Raft Microdomains.
Tabbasum, Valentina G
The Journal of membrane biology
MetadataShow full item record
Tabbasum, V. G., & Cooper, D. (2019). Structural and Functional Determinants of AC8 Trafficking, Targeting and Responsiveness in Lipid Raft Microdomains.. The Journal of membrane biology, 252 (2-3), 159-172. https://doi.org/10.1007/s00232-019-00060-x
The fidelity of cAMP in controlling numerous cellular functions rests crucially on the precise organization of cAMP microdomains that are sustained by the scaffolding properties of adenylyl cyclase. Earlier studies suggested that AC8 enriches in lipid rafts where it interacts with cytoskeletal elements. However, these are not stable structures and little is known about the dynamics of AC8 secretion and its interactions. The present study addresses the role of the cytoskeleton in maintaining the AC8 microenvironment, particularly in the context of the trafficking route of AC8 and its interaction with caveolin1. Here, biochemical and live-cell imaging approaches expose a complex, dynamic interaction between AC8 and caveolin1 that affects AC8 processing, targeting and responsiveness in plasma membrane lipid rafts. Site-directed mutagenesis and pharmacological approaches reveal that AC8 is processed with complex N-glycans and associates with lipid rafts en route to the plasma membrane. A dynamic picture emerges of the trafficking and interactions of AC8 while travelling to the plasma membrane, which are key to the organization of the AC8 microdomain.
Membrane Microdomains, Cytoskeleton, Humans, Brefeldin A, beta-Cyclodextrins, Guanine Nucleotide Exchange Factors, Bacterial Proteins, Luminescent Proteins, Green Fluorescent Proteins, Recombinant Fusion Proteins, RNA, Small Interfering, Cyclic AMP, Mutagenesis, Site-Directed, Gene Expression, Protein Transport, Genes, Reporter, Caveolin 1, Thiazolidines, HEK293 Cells, Adenylyl Cyclases, Bridged Bicyclo Compounds, Heterocyclic
External DOI: https://doi.org/10.1007/s00232-019-00060-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/289457
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
Recommended or similar items
The following licence files are associated with this item: