دورية أكاديمية
أعرض في EDS

Functional Interactions between BK Ca α -Subunit and Annexin A5: Implications in Apoptosis.

التفاصيل البيبلوغرافية
العنوان: Functional Interactions between BK Ca α -Subunit and Annexin A5: Implications in Apoptosis.
المؤلفون: Brazier SP; Division of Pathophysiology and Repair, School of Biosciences, Sir Martin Evans Building, Museum Avenue, Cardiff University, Cardiff CF10 3AX, UK., Telezhkin V; Division of Pathophysiology and Repair, School of Biosciences, Sir Martin Evans Building, Museum Avenue, Cardiff University, Cardiff CF10 3AX, UK., Kemp PJ; Division of Pathophysiology and Repair, School of Biosciences, Sir Martin Evans Building, Museum Avenue, Cardiff University, Cardiff CF10 3AX, UK.
المصدر: Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2016; Vol. 2016, pp. 1607092. Date of Electronic Publication: 2016 Sep 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Hindawi Pub. Corp Country of Publication: United States NLM ID: 101479826 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1942-0994 (Electronic) Linking ISSN: 19420994 NLM ISO Abbreviation: Oxid Med Cell Longev Subsets: MEDLINE
أسماء مطبوعة: Publication: 2011- : New York : Hindawi Pub. Corp.
Original Publication: 2008-2010: Austin, TX : Landes Bioscience
مواضيع طبية MeSH: Apoptosis*, Annexin A5/*metabolism , Large-Conductance Calcium-Activated Potassium Channels/*metabolism, Annexin A5/antagonists & inhibitors ; Annexin A5/genetics ; Calcium/metabolism ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Membrane/metabolism ; HEK293 Cells ; Humans ; Immunohistochemistry ; Immunoprecipitation ; Large-Conductance Calcium-Activated Potassium Channels/chemistry ; Large-Conductance Calcium-Activated Potassium Channels/genetics ; Microscopy, Confocal ; Patch-Clamp Techniques ; Protein Subunits/chemistry ; Protein Subunits/genetics ; Protein Subunits/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism
مستخلص: Proteomic studies have suggested a biochemical interaction between α subunit of the large conductance, voltage- and Ca 2+ -activated potassium channel (BK Ca α ), 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 BK Ca α contains both Ca 2+ -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 BK Ca α expressing HEK 293 cells. The functional consequences of ANXA5 partnership with BK Ca α were striking, with ANXA5 knockdown causing an increase and ANXA5 overexpression causing a decrease, in single BK Ca channel Ca 2+ -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 Ca 2+ influx and augmented activation of caspases.
Competing Interests: The authors declare no competing interests.
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المشرفين على المادة: 0 (Annexin A5)
0 (Large-Conductance Calcium-Activated Potassium Channels)
0 (Protein Subunits)
0 (RNA, Small Interfering)
EC 3.4.22.- (Caspase 3)
EC 3.4.22.- (Caspase 7)
SY7Q814VUP (Calcium)
تواريخ الأحداث: Date Created: 20161015 Date Completed: 20170308 Latest Revision: 20181113
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5055951
DOI: 10.1155/2016/1607092
PMID: 27738490
قاعدة البيانات: MEDLINE
الوصف
تدمد:1942-0994
DOI:10.1155/2016/1607092