Optical Control of Phosphatidic Acid Signaling

Reika Tei, Johannes Morstein, Andrej Shemet, Dirk Trauner, Jeremy M. Baskin

Research output: Contribution to journalArticlepeer-review

Abstract

Phosphatidic acids (PAs) are glycerophospholipids that regulate key cell signaling pathways governing cell growth and proliferation, including the mTOR and Hippo pathways. Their acyl chains vary in tail length and degree of saturation, leading to marked differences in the signaling functions of different PA species. For example, in mTOR signaling, saturated forms of PA are inhibitory, whereas unsaturated forms are activating. To enable rapid control over PA signaling, we describe here the development of photoswitchable analogues of PA, termed AzoPA and dAzoPA, that contain azobenzene groups in one or both lipid tails, respectively. These photolipids enable optical control of their tail structure and can be reversibly switched between a straight trans form and a relatively bent cis form. We found that cis-dAzoPA selectively activates mTOR signaling, mimicking the bioactivity of unsaturated forms of PA. Further, in the context of Hippo signaling, whose growth-suppressing activity is blocked by PA, we found that the cis forms of both AzoPA and dAzoPA selectively inhibit this pathway. Collectively, these photoswitchable PA analogues enable optical control of mTOR and Hippo signaling, and we envision future applications of these probes to dissect the pleiotropic effects of physiological and pathological PA signaling.

Original languageEnglish (US)
Pages (from-to)1205-1215
Number of pages11
JournalACS Central Science
Volume7
Issue number7
DOIs
StatePublished - Jul 28 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Fingerprint

Dive into the research topics of 'Optical Control of Phosphatidic Acid Signaling'. Together they form a unique fingerprint.

Cite this