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Shedding Light on Phosphatidic Acid Signaling with Chemical Tools
Author(s) -
Baskin Jeremy M.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00198
Subject(s) - phosphatidic acid , phospholipase d , second messenger system , organelle , chemistry , endosome , microbiology and biotechnology , cell signaling , lipid signaling , intracellular , signal transduction , biochemistry , phospholipid , computational biology , biology , enzyme , membrane
The fidelity of intracellular signaling pathways requires that cells control the production of signaling agents in space and in time. Phosphatidic acid (PA) is both a central phospholipid biosynthetic intermediate and a multifunctional lipid second messenger produced at several discrete subcellular locations. The modes of action of PA can differ based on upstream stimulus, biosynthetic source, and site of production. How cells regulate the local production of PA to direct diverse signaling outcomes remains elusive. To begin to unravel these questions, we have focused our efforts on improving and expanding the toolkit for both visualizing and perturbing cellular PA production, with spatiotemporal precision. Toward the first goal, we have harnessed the exquisite selectivity of chemoenzymatic labeling and click chemistry tagging to develop a method for directly visualizing PA production by phospholipase D (PLD) enzymes. This method, termed IMPACT for Imaging PLD Activity with Clickable Alcohols via Transphosphatidylation, has revealed sites of PLD‐mediated PA signaling elicited by diverse physiological stimuli and features subcellular, organelle‐level resolution. To complement these tools for visualizing PA production, we have also generated a suite of light‐controllable, optogenetic PLDs to precisely generate tunable amounts of PA, on demand, at specific organelle membranes. Collectively, these new approaches represent powerful and precise approaches for revealing spatiotemporally defined functions of PA in response to physiological and pathological stimuli. Support or Funding Information NIH R00GM110121, NIH R01GM131101, NSF CAREER CHE‐1749919, Beckman Young Investigator, Sloan Research Fellowship