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Identification of intracellular cavin target proteins reveals cavin-PP1alpha interactions regulate apoptosis

By Kerrie-Ann McMahon, Yeping Wu, Yann Gambin, Emma Sierecki, Vikas A. Tillu, Thomas Hall, Nick Martel, Satomi Okano, Shayli Varasteh Moradi, Jayde E. Ruelcke, Charles Ferguson, Alpha S. Yap, Kirill Alexandrov, Michelle M. Hill and Robert G. Parton


Caveolae are specialized domains of the plasma membrane. Formation of these invaginations is dependent on the expression of Caveolin-1 or -3 and proteins of the cavin family. In response to stress, caveolae disassemble and cavins are released from caveolae, allowing cavins to potentially interact with intracellular targets. Here, we describe the intracellular (non-plasma membrane) cavin interactome using biotin affinity proteomics and mass spectrometry. We validate 47 potential cavin-interactor proteins using a cell-free expression system and protein-protein binding assays. These data, together with pathway analyses, reveal unknown roles for cavin proteins in metabolism and stress signaling. We validated the interaction between one candidate interactor protein, protein phosphatase 1 alpha (PP1α), and Cavin-1 and -3 and show that UV treatment causes release of Cavin3 from caveolae allowing interaction with, and inhibition of, PP1α. This interaction increases H2AX phosphorylation to stimulate apoptosis, identifying a pro-apoptotic signaling pathway from surface caveolae to the nucleus

Topics: General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry, 1300 Biochemistry, Genetics and Molecular Biology, 1600 Chemistry, 3100 Physics and Astronomy
Publisher: Nature Publishing Group
Year: 2019
DOI identifier: 10.1038/s41467-019-11111-1
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