Both IRBIT and long-IRBIT bind to and coordinately regulate Cl/HCO3 exchanger AE2 activity through modulating the lysosomal degradation of AE2

Ryo Itoh, Naoya Hatano, Momoko Murakami, Kosuke Mitsumori, Satoko Kawasaki, Tomoka Wakagi, Yoshino Kanzaki, Hiroyuki Kojima, Katsuhiro Kawaai, Katsuhiko Mikoshiba, Koichi Hamada, Akihiro Mizutani

研究成果: Article査読

抄録

Anion exchanger 2 (AE2) plays crucial roles in regulating cell volume homeostasis and cell migration. We found that both IRBIT and Long-IRBIT (L-IRBIT) interact with anion exchanger 2 (AE2). The interaction occurred between the conserved AHCY-homologous domain of IRBIT/L-IRBIT and the N-terminal cytoplasmic region of AE2. Interestingly, AE2 activity was reduced in L-IRBIT KO cells, but not in IRBIT KO cells. Moreover, AE2 activity was slightly increased in IRBIT/L-IRBIT double KO cells. These changes in AE2 activity resulted from changes in the AE2 expression level of each mutant cell, and affected the regulatory volume increase and cell migration. The activity and expression level of AE2 in IRBIT/L-IRBIT double KO cells were downregulated if IRBIT, but not L-IRBIT, was expressed again in the cells, and the downregulation was cancelled by the co-expression of L-IRBIT. The mRNA levels of AE2 in each KO cell did not change, and the downregulation of AE2 in L-IRBIT KO cells was inhibited by bafilomycin A1. These results indicate that IRBIT binding facilitates the lysosomal degradation of AE2, which is inhibited by coexisting L-IRBIT, suggesting a novel regulatory mode of AE2 activity through the binding of two homologous proteins with opposing functions.

本文言語English
論文番号5990
ジャーナルScientific reports
11
1
DOI
出版ステータスPublished - 2021 12

ASJC Scopus subject areas

  • 一般

フィンガープリント

「Both IRBIT and long-IRBIT bind to and coordinately regulate Cl<sup>−</sup>/HCO<sub>3</sub><sup>−</sup> exchanger AE2 activity through modulating the lysosomal degradation of AE2」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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