Academic Journal

A‐Kinase anchoring protein 2 (AKAP2) and Pendrin; cross‐talk between cell signaling and renal physiology

التفاصيل البيبلوغرافية
العنوان: A‐Kinase anchoring protein 2 (AKAP2) and Pendrin; cross‐talk between cell signaling and renal physiology
المؤلفون: Belaid, Houwayda, Wang, Dongmei, Mendes Carraco, Ana, Li, Na, Van Bemmelen, Miguel, Diviani, Dario, Staub, Olivier
المساهمون: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
المصدر: The FASEB Journal ; volume 36, issue S1 ; ISSN 0892-6638 1530-6860
بيانات النشر: Wiley
سنة النشر: 2022
المجموعة: Wiley Online Library (Open Access Articles via Crossref)
الوصف: Kidney tubules play a pivotal role in the maintenance of body fluid homeostasis and pH regulation. Accordingly, kidney disorders are known to be strongly associated with hypertension and acid‐base imbalance. In the kidney, the intercalated cells of the nephron are the main site of acid‐base balance: type A are acid‐secreting whereas type B are base‐secreting. The chloride bicarbonate exchanger Pendrin is present in type B intercalated cells and participates actively in regulating blood pressure and NaCl balance. It is still not entirely deciphered how Pendrin activity is regulated; nevertheless, it was previously demonstrated that Pendrin is regulated by c‐AMP/Protein Kinase A (PKA) signaling pathway. Consequently, in this study, our hypothesis is that the A‐Kinase anchoring protein 2 (AKAP2), strongly expressed in the kidney, regulates in time and space the intracellular signal transduction. In order to investigate AKAP2 involvement in Pendrin regulation and trafficking to the apical plasma membrane, we generated an inducible and nephron‐specific Akap2 Pax8/LC1 mice knockout model. By confocal microscopy, fluorescent immunostaining on kidney tissue sections showed that AKAP2 is present in the tubules and most importantly colocalizes with Pendrin at the apical plasma membrane of the intercalated cells. To show that Pendrin and AKAP2 are interacting, we used the Proximity Ligation Assay (PLA) and, positively, we could reveal the association between the two proteins. The latter finding was also confirmed in vitro taking advantage of the Opossum Kidney Cell line (OKP) stably expressing Pendrin and co‐transfected with AKAP2, we could co‐immunoprecipitate Pendrin and AKAP2 after crosslinking on live cells. Fluorescent immunostaining in Akap2 Pax8/LC1 show that Pendrin tends to be shifted from the apical membrane (seen in control mice) to intracellular compartments. In conclusion, our data suggest that AKAP2 and Pendrin are interacting, and AKAP2 may play a key role in Pendrin trafficking to the apical plasma ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1096/fasebj.2022.36.s1.r2873
الاتاحة: http://dx.doi.org/10.1096/fasebj.2022.36.s1.r2873
Rights: http://onlinelibrary.wiley.com/termsAndConditions#vor
رقم الانضمام: edsbas.1E8195CB
قاعدة البيانات: BASE
الوصف
DOI:10.1096/fasebj.2022.36.s1.r2873