リソホスファチジン酸シグナル伝達の光制御

Optical Control of Lysophosphatidic Acid Signaling.

• Johannes Morstein
• Mélanie A Dacheux
• Derek D Norman
• Andrej Shemet
• Prashant C Donthamsetti
• Mevlut Citir
• James A Frank
• Carsten Schultz
• Ehud Y Isacoff
• Abby L Parrill
• Gabor J Tigyi
• Dirk Trauner

抄録

リゾホスファチジン酸（LPA）は、細胞外シグナル伝達物質として作用し、リゾホスファチジン酸受容体（LPA）ファミリーを活性化するリン脂質である。これらのGタンパク質共役型受容体（GPCR）は広く発現しており、神経系、循環器系、生殖器系、消化器系、肺系と同様に発生においても特に重要な役割を果たしている。本研究では、アシル鎖に埋め込まれたアゾベンゼン光スイッチを含むLPAの光スイッチング可能な類似体を報告する。

Lysophosphatidic acid (LPA) is a phospholipid that acts as an extracellular signaling molecule and activates the family of lysophosphatidic acid receptors (LPA). These G protein-coupled receptors (GPCRs) are broadly expressed and are particularly important in development as well as in the nervous, cardiovascular, reproductive, gastrointestinal, and pulmonary systems. Here, we report on a photoswitchable analogue of LPA, termed , which contains an azobenzene photoswitch embedded in the acyl chain. enables optical control of LPA receptor activation, shown through its ability to rapidly control LPA-evoked increases in intracellular Ca levels. shows greater activation of LPA receptors in its light-induced -form than its dark-adapted (or 460 nm light-induced) -form. enabled the optical control of neurite retraction through its activation of the LPA receptor.