Caveolin-Na/K-ATPase interactions: Role of transmembrane topology in non-genomic steroid signal transduction

详细信息    查看全文

• 作者：Gene A. Morrill ; Adele B. Kostellow ; Amir Askari
• 关键词：Na/K-ATPase ; Caveolin ; Protein topology ; Progesterone ; Ouabain ; Meiosis
• 刊名：Steroids
• 出版年：2012
• 出版时间：September, 2012
• 年：2012
• 卷：77
• 期：11
• 页码：1160-1168
• 全文大小：1108 K

文摘

Progesterone and its polar metabolite(s) trigger the meiotic divisions in the amphibian oocyte through a non-genomic signaling system at the plasma membrane. Published site-directed mutagenesis studies of ouabain binding and progesterone-ouabain competition studies indicate that progesterone binds to a 23 amino acid extracellular loop of the plasma membrane ¦Á-subunit of Na/K-ATPase. Integral membrane proteins such as caveolins are reported to form Na/K-ATPase-peptide complexes essential for signal transduction. We have characterized the progesterone-induced Na/K-ATPase-caveolin (CAV-1)-steroid 5¦Á-reductase interactions initiating the meiotic divisions. Peptide sequence analysis algorithms indicate that CAV-1 contains two plasma membrane spanning helices, separated by as few as 1-2 amino acid residues at the cell surface. The CAV-1 scaffolding domain, reported to interact with CAV-1 binding (CB) motifs in signaling proteins, overlaps transmembrane (TM) helix 1. The ¦Á-subunit of Na/K-ATPase (10 TM helices) contains double CB motifs within TM-1 and TM-10. Steroid 5¦Á-reductase (6 TM helices), an initial step in polar steroid formation, contains CB motifs overlapping TM-1 and TM-6. Computer analysis predicts that interaction between antipathic strands may bring CB motifs and scaffolding domains into close proximity, initiating allostearic changes. Progesterone binding to the ¦Á-subunit may thus facilitate CB motif:CAV-1 interaction, which in turn induces helix-helix interaction and generates both a signaling cascade and formation of polar steroids.