2010年6月
Mechanism for the regulation of mammalian cGMP phosphodiesterase6. 1: Identification of its inhibitory subunit complexes and their roles
MOLECULAR AND CELLULAR BIOCHEMISTRY
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- 巻
- 339
- 号
- 1-2
- 開始ページ
- 215
- 終了ページ
- 233
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1007/s11010-010-0387-8
- 出版者・発行元
- SPRINGER
Cyclic GMP phosphodiesterase (PDE) in bovine rod photoreceptor outer segments (OS) comprises a catalytic subunit complex (P alpha beta) and two inhibitory subunits (P gamma) and is regulated by the alpha subunit of transducin (T alpha). Here, we show an overall mechanism for PDE regulation by identifying P gamma complexes in OS homogenates prepared with an isotonic buffer. Before T alpha activation, three P gamma complexes exist in the soluble fraction. Complex a, a minor complex, contains P alpha beta, T alpha, and a protein named P delta. Complex b, P alpha beta gamma gamma (b) , has a PDE activity similar to that of membranous P alpha beta gamma gamma, P alpha beta gamma gamma (M) , and its level, although its large portion is P delta-free, is estimated to be 20-30% of the total P alpha beta gamma gamma. Complex c, (P gamma center dot GDP-T alpha) (2) (c) , appears to be a dimer of P gamma center dot GDP-T alpha. Upon T alpha activation, (1) complex a stays unchanged, (2) P alpha beta gamma gamma (b) binds to membranes, (3) the level of (P gamma center dot GDP-T alpha) (2) (c) is reduced as its GTP-form is produced, (4) complex d, P gamma center dot GTP-T alpha (d) , is formed on membranes and its substantial amount is released to the soluble fraction, and (5) membranous P alpha beta gamma gamma, P alpha beta gamma gamma (M) and/or P alpha beta gamma gamma (b) , becomes P gamma-depleted. These observations indicate that P gamma as a complex with GTP-T alpha dissociates from P alpha beta gamma gamma on membranes and is released to the soluble fraction and that P gamma-depleted PDE is the GTP-T alpha-activated PDE. After GTP hydrolysis, both (P gamma center dot GDP-T alpha) (2) (c) and P gamma center dot GDP-T alpha (d) , without liberating P gamma, deactivate P gamma-depleted PDE. The preferential order to be used for the deactivation is membranous P gamma center dot GDP-T alpha (d) , solubilized P gamma center dot GDP-T alpha (d) and (P gamma center dot GDP-T alpha) (2) (c) . Release of P gamma center dot GTP-T alpha complexes to the soluble fraction is relevant to light adaptation.
- リンク情報
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- DOI
- https://doi.org/10.1007/s11010-010-0387-8
- CiNii Articles
- http://ci.nii.ac.jp/naid/80021023838
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/20151179
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000277432000022&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1007/s11010-010-0387-8
- ISSN : 0300-8177
- CiNii Articles ID : 80021023838
- PubMed ID : 20151179
- Web of Science ID : WOS:000277432000022