Highlighted paper selected by editor-in-chief: Nedd4-interacting protein 2, a short half-life membrane protein degraded in lysosomes, negatively controls down-regulation of connexin43

DOI Web Site Web Site 被引用文献2件 参考文献31件
  • Ohzono Chiho
    Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University
  • Etoh Sachise
    Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University
  • Matsumoto Masaki
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University
  • Nakayama Keiichi I
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University
  • Hirota Yuko
    Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University
  • Tanaka Yoshitaka
    Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University
  • Fujita Hideaki
    Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University

書誌事項

タイトル別名
  • Nedd4-Interacting Protein 2, a Short Half-life Membrane Protein Degraded in Lysosomes, Negatively Controls Down-Regulation of Connexin43

この論文をさがす

抄録

Nedd4-interacting protein 2 (NDFIP2) has three transmembrane domains and interacts with multiple Nedd4 family ubiquitin ligases through polyprolinetyrosine (PY) motifs located in its N-terminal cytoplasmic domain. It has been postulated that NDFIP2 acts as an adaptor for the ubiquitylation of substrates with Nedd4 ubiquitin ligase. However, whether NDFIP2 promotes or inhibits the ubiquitylation of Nedd4 substrates is still under debate. We show here that although NDFIP2 is detected in the Golgi/trans-Golgi network (TGN) area, it is rapidly delivered to and degraded in lysosomes with its half-life ca. 1.5 h. Intriguingly, knockdown (KD) of NDFIP2 with small interfering RNA (siRNA) impaired both the formation and function of gap junctions. Indeed, KD of NDFIP2 destabilized the gap junction protein connexin43 that contains PY motif. In support of this, overexpression of NDFIP2 stabilized connexin43 and enhanced the formation of gap junctions. Furthermore, the PY motifs of NDFIP2, which are required for its interaction with Nedd4, Atrophin-1 interacting protein (AIP) 4 (AIP4)/Itch, and AIP2/WWP2, were necessary for the targeting of NDFIP2 to lysosomes and/or the stability of connexin43 and gap junctions. Collectively these findings suggest that NDFIP2 may inhibit the Nedd4-dependent ubiquitylation of membrane proteins containing PY motifs, such as connexin43, in a competitive manner.

収録刊行物

被引用文献 (2)*注記

もっと見る

参考文献 (31)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ