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KCa1.1 channels regulate β 1 ‐integrin function and cell adhesion in rheumatoid arthritis fibroblast‐like synoviocytes
Author(s) -
Tanner Mark R.,
Pennington Michael W.,
Laragione Teresina,
Gulko Pércio S.,
Beeton Christine
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601097r
Subject(s) - integrin , microbiology and biotechnology , chemistry , cell adhesion molecule , regulator , cell adhesion , adhesion , cell , biology , biochemistry , organic chemistry , gene
Large‐conductance calcium‐activated potassium channel (KCa1.1; BK, Slo1, MaxiK, KCNMA1) is the predominant potassium channel expressed at the plasma membrane of rheumatoid arthritis fibroblast‐like synoviocytes (RA‐FLSs) isolated from the synovium of patients with RA. It is a critical regulator of RA‐FLS migration and invasion and therefore represents an attractive target for the therapy of RA. However, the molecular mechanisms by which KCa1.1 regulates RA‐FLS invasiveness have remained largely unknown. Here, we demonstrate that KCa1.1 regulates RA‐FLS adhesion through controlling the plasma membrane expression and activation of β 1 integrins, but not α 4 , α 5 , or α 6 integrins. Blocking KCa1.1 disturbs calcium homeostasis, leading to the sustained phosphorylation of Akt and the recruitment of talin to β 1 integrins. Interestingly, the pore‐forming α subunit of KCa1.1 coimmunoprecipitates with β 1 integrins, suggesting that this physical association underlies the functional interaction between these molecules. Together, these data outline a new signaling mechanism by which KCa1.1 regulates β 1 integrin function and therefore invasiveness of RA‐FLSs.—Tanner, M. R., Pennington, M. W., Laragione, T., Gulko, P. S., Beeton, C. KCa1.1 channels regulate β 1 ‐integrin function and cell adhesion in rheumatoid arthritis fibroblast‐like synoviocytes. FASEB J . 31, 3309–3320 (2017). www.fasebj.org