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Functional Interactions between BKCaα-Subunit and Annexin A5: Implications in Apoptosis

Lookup NU author(s): Dr Seva TelezhkinORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Proteomic studies have suggested a biochemical interaction between α subunit of the large conductance, voltage- and Ca2+-activated potassium channel (BKCaα), and annexin A5 (ANXA5), which we verify here by coimmunoprecipitation and double labelling immunocytochemistry. The observation that annexin is flipped to the outer membrane leaflet of the plasma membrane during apoptosis, together with the knowledge that the intracellular C-terminal of BKCaα contains both Ca2+-binding and a putative annexin-binding motif, prompted us to investigate the functional consequences of this protein partnership to cell death. Membrane biotinylation demonstrated that ANXA5 was flipped to the outer membrane leaflet of HEK 293 cells early in serum deprivation-evoked apoptosis. As expected, serum deprivation caused caspase-3/7 activation and this was accentuated in BKCaα expressing HEK 293 cells. The functional consequences of ANXA5 partnership with BKCaα were striking, with ANXA5 knockdown causing an increase and ANXA5 overexpression causing a decrease, in single BKCa channel Ca2+-sensitivity, measured in inside-out membrane patches by patch-clamp. Taken together, these data suggest a novel model of the early stages of apoptosis where membrane flippage results in removal of the inhibitory effect of ANXA5 on K+ channel activity with the consequent amplification of Ca2+ influx and augmented activation of caspases.

Publication metadata

Author(s): Brazier SP, Telezhkin V, Kemp PJ

Publication type: Article

Publication status: Published

Journal: Oxidative Medicine and Cellular Longevity

Year: 2016

Volume: 2016

Print publication date: 16/09/2016

Acceptance date: 10/07/2016

Date deposited: 09/03/2017

ISSN (print): 1942-0900

ISSN (electronic): 1942-0994

Publisher: Hindawi


DOI: 10.1155/2016/1607092

PubMed id: 27738490


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