Abstract β-catenin, a multifunctional protein expressed in all tissues including the heart stimulates the expression of several genes important for cell proliferation. Signaling involving ß-catenin participates in directing cardiac development and in the pathophysiology of cardiac hypertrophy. Nothing is known, however, on the role of β-catenin in the regulation of cardiac ion channels. The present study explored the functional interaction of β-catenin and KCNE1/KCNQ1, the K(+) channel complex underlying the slowly activating outwardly rectifying K(+) current. To this end, KCNE1/KCNQ1 was expressed in Xenopus oocytes with and without β-catenin and the depolarization (up to + 80 mV) induced current (I(Ks)) was determined using the two-electrode voltage clamp. As a result, β-catenin enhanced I(Ks) by 30%. The effect of β-catenin on I(Ks) was not affected by actinomycin D (10 μM), an inhibitor of transcription, indicating that β-catenin was not effective as transcription factor. Confocal microscopy revealed that β-catenin enhanced the KCNE1/KCNQ1 protein abundance in the cell membrane. Exposure of the oocytes to brefeldin A (5 μM), an inhibitor of vesicle insertion, was followed by a decline of I(Ks), which was then similar in oocytes expressing KCNE1/KCNQ1 together with β-catenin and in oocytes expressing KCNE1/KCNQ1 alone. In conclusion, β-catenin enhances I(Ks) by increasing the KCNE1/KCNQ1 protein abundance in the cell membrane, an effect requiring vesicle insertion into the cell membrane.

Regulation of KCNQ1/KCNE1 by β-catenin.

FAGGIO, Caterina;
2012-01-01

Abstract

Abstract β-catenin, a multifunctional protein expressed in all tissues including the heart stimulates the expression of several genes important for cell proliferation. Signaling involving ß-catenin participates in directing cardiac development and in the pathophysiology of cardiac hypertrophy. Nothing is known, however, on the role of β-catenin in the regulation of cardiac ion channels. The present study explored the functional interaction of β-catenin and KCNE1/KCNQ1, the K(+) channel complex underlying the slowly activating outwardly rectifying K(+) current. To this end, KCNE1/KCNQ1 was expressed in Xenopus oocytes with and without β-catenin and the depolarization (up to + 80 mV) induced current (I(Ks)) was determined using the two-electrode voltage clamp. As a result, β-catenin enhanced I(Ks) by 30%. The effect of β-catenin on I(Ks) was not affected by actinomycin D (10 μM), an inhibitor of transcription, indicating that β-catenin was not effective as transcription factor. Confocal microscopy revealed that β-catenin enhanced the KCNE1/KCNQ1 protein abundance in the cell membrane. Exposure of the oocytes to brefeldin A (5 μM), an inhibitor of vesicle insertion, was followed by a decline of I(Ks), which was then similar in oocytes expressing KCNE1/KCNQ1 together with β-catenin and in oocytes expressing KCNE1/KCNQ1 alone. In conclusion, β-catenin enhances I(Ks) by increasing the KCNE1/KCNQ1 protein abundance in the cell membrane, an effect requiring vesicle insertion into the cell membrane.
2012
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/1967821
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 11
social impact