Cargando…

Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling

The simple structure of phosphatidic acid (PA) belies its complex biological functions as both a key phospholipid biosynthetic intermediate and a potent signaling molecule. In the latter role, PA controls processes including vesicle trafficking, actin dynamics, cell growth, and migration. However, e...

Descripción completa

Detalles Bibliográficos
Autores principales: Tei, Reika, Baskin, Jeremy M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006657/
https://www.ncbi.nlm.nih.gov/pubmed/35276134
http://dx.doi.org/10.1016/j.jbc.2022.101810
_version_ 1784686711561781248
author Tei, Reika
Baskin, Jeremy M.
author_facet Tei, Reika
Baskin, Jeremy M.
author_sort Tei, Reika
collection PubMed
description The simple structure of phosphatidic acid (PA) belies its complex biological functions as both a key phospholipid biosynthetic intermediate and a potent signaling molecule. In the latter role, PA controls processes including vesicle trafficking, actin dynamics, cell growth, and migration. However, experimental methods to decode the pleiotropy of PA are sorely lacking. Because PA metabolism and trafficking are rapid, approaches to accurately visualize and manipulate its levels require high spatiotemporal precision. Here, we describe recent efforts to create a suite of chemical tools that enable imaging and perturbation of PA signaling. First, we describe techniques to visualize PA production by phospholipase D (PLD) enzymes, which are major producers of PA, called Imaging Phospholipase D Activity with Clickable Alcohols via Transphosphatidylation (IMPACT). IMPACT harnesses the ability of endogenous PLD enzymes to accept bioorthogonally tagged alcohols in transphosphatidylation reactions to generate functionalized reporter lipids that are subsequently fluorescently tagged via click chemistry. Second, we describe two light-controlled approaches for precisely manipulating PA signaling. Optogenetic PLDs use light-mediated heterodimerization to recruit a bacterial PLD to desired organelle membranes, and photoswitchable PA analogs contain azobenzene photoswitches in their acyl tails, enabling molecular shape and bioactivity to be controlled by light. We highlight select applications of these tools for studying GPCR–G(q) signaling, discovering regulators of PLD signaling, tracking intracellular lipid transport pathways, and elucidating new oncogenic signaling roles for PA. We envision that these chemical tools hold promise for revealing many new insights into lipid signaling pathways.
format Online
Article
Text
id pubmed-9006657
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-90066572022-04-18 Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling Tei, Reika Baskin, Jeremy M. J Biol Chem ASBMB Award Article The simple structure of phosphatidic acid (PA) belies its complex biological functions as both a key phospholipid biosynthetic intermediate and a potent signaling molecule. In the latter role, PA controls processes including vesicle trafficking, actin dynamics, cell growth, and migration. However, experimental methods to decode the pleiotropy of PA are sorely lacking. Because PA metabolism and trafficking are rapid, approaches to accurately visualize and manipulate its levels require high spatiotemporal precision. Here, we describe recent efforts to create a suite of chemical tools that enable imaging and perturbation of PA signaling. First, we describe techniques to visualize PA production by phospholipase D (PLD) enzymes, which are major producers of PA, called Imaging Phospholipase D Activity with Clickable Alcohols via Transphosphatidylation (IMPACT). IMPACT harnesses the ability of endogenous PLD enzymes to accept bioorthogonally tagged alcohols in transphosphatidylation reactions to generate functionalized reporter lipids that are subsequently fluorescently tagged via click chemistry. Second, we describe two light-controlled approaches for precisely manipulating PA signaling. Optogenetic PLDs use light-mediated heterodimerization to recruit a bacterial PLD to desired organelle membranes, and photoswitchable PA analogs contain azobenzene photoswitches in their acyl tails, enabling molecular shape and bioactivity to be controlled by light. We highlight select applications of these tools for studying GPCR–G(q) signaling, discovering regulators of PLD signaling, tracking intracellular lipid transport pathways, and elucidating new oncogenic signaling roles for PA. We envision that these chemical tools hold promise for revealing many new insights into lipid signaling pathways. American Society for Biochemistry and Molecular Biology 2022-03-08 /pmc/articles/PMC9006657/ /pubmed/35276134 http://dx.doi.org/10.1016/j.jbc.2022.101810 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle ASBMB Award Article
Tei, Reika
Baskin, Jeremy M.
Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling
title Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling
title_full Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling
title_fullStr Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling
title_full_unstemmed Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling
title_short Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling
title_sort click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling
topic ASBMB Award Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006657/
https://www.ncbi.nlm.nih.gov/pubmed/35276134
http://dx.doi.org/10.1016/j.jbc.2022.101810
work_keys_str_mv AT teireika clickchemistryandoptogeneticapproachestovisualizeandmanipulatephosphatidicacidsignaling
AT baskinjeremym clickchemistryandoptogeneticapproachestovisualizeandmanipulatephosphatidicacidsignaling