Fatty-acyl chain profiles of cellular phosphoinositides

Traynor‐Kaplan, Alexis; Kruse, Martin; Dickson, Eamonn J.; Dai, Gucan; Vivas, Oscar; Hou, Yu; Whittington, Dale; Hille, Bertil

doi:10.1016/j.bbalip.2017.02.002

Cited by 92 publications

(129 citation statements)

References 64 publications

Supporting

Mentioning

125

Contrasting

Order By: Relevance

“…In this case, basal PIP 2 may suffice to localize GRKs. Although it generates diffusible G βγ , the WT M 1 R is phosphorylated by CK2 instead of GRK2/3 possibly because it substantially reduces plasma membrane PIP 2 and PIP with the strong stimuli that we use (20,45).…”

Section: Discussionmentioning

confidence: 99%

Muscarinic receptor regulates extracellular signal regulated kinase by two modes of arrestin binding

Jung

Kushmerick

Seo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Binding of agonists to G-protein-coupled receptors (GPCRs) activates heterotrimeric G proteins and downstream signaling. Agonistbound GPCRs are then phosphorylated by protein kinases and bound by arrestin to trigger desensitization and endocytosis. Arrestin plays another important signaling function. It recruits and regulates activity of an extracellular signal-regulated kinase (ERK) cascade. However, molecular details and timing of ERK activation remain fundamental unanswered questions that limit understanding of how arrestin-dependent GPCR signaling controls cell functions.Here we validate and model a system that tracks the dynamics of interactions of arrestin with receptors and of ERK activation using optical reporters. Our intermolecular FRET measurements in living cells are consistent with β-arrestin binding to M 1 muscarinic acetylcholine receptors (M 1 Rs) in two different binding modes, transient and stable. The stable mode persists for minutes after agonist removal. The choice of mode is governed by phosphorylation on key residues in the third intracellular loop of the receptor. We detect a similar intramolecular conformational change in arrestin in either binding mode. It develops within seconds of arrestin binding to the M 1 receptor, and it reverses within seconds of arrestin unbinding from the transient binding mode. Furthermore, we observed that, when stably bound to phosphorylated M 1 R, β-arrestin scaffolds and activates MEK-dependent ERK. In contrast, when transiently bound, β-arrestin reduces ERK activity via recruitment of a protein phosphatase. All this ERK signaling develops at the plasma membrane. In this scaffolding hypothesis, a shifting balance between the two arrestin binding modes determines the degree of ERK activation at the membrane.arrestin | GPCR | ERK | muscarinic receptor | receptor kinase A rrestin plays a fundamental role in the negative regulation of G-protein-coupled receptors (GPCRs) signaling because its binding to GPCRs hinders G-protein association with the receptors (1-5). Arrestin further recruits adaptor proteins and clathrin for the internalization and desensitization of the receptor (6). Additional functions have been suggested, with β-arrestin producing its own signaling through interactions with other effectors (7-9). For example, β-arrestin has binding sites for cRaf (MAPK kinase kinase), MEK (MAPK kinase), and ERK (MAPK) that mediate a signaling cascade for cell proliferation, cell migration, and actin dynamics after GPCR activation (10-13). Conventionally, MEK-dependent ERK signaling is described as involving GPCR-arrestin complexes on intracellular compartments such as endosomal vesicles (10, 14-16). However, whether similar complexes at the plasma membrane might trigger ERK signaling remains unknown. Electron microscope images of arrestin-receptor complexes together with modeling suggest that β-arrestin binds in two different modes, called transient binding and stable binding, to chimeric β 2 adrenergic receptors (β 2 -AR) containing the C terminus of vasopre...

show abstract

Section: Discussionmentioning

confidence: 99%

Muscarinic receptor regulates extracellular signal regulated kinase by two modes of arrestin binding

Jung

Kushmerick

Seo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…There have been a few studies with either supplementation of arachidonate or other PUFAs and the effect of serum starvation on cellular function (18). In such studies a remarkable effect of depletion of arachidonic acid has been noted (19). Current recommendations for cell culture suggest changing culture media (resupply of PUFAs) only as frequently as 3 days with no suggestion that this period of time could lead to important biochemical changes by depletion of PUFAs (20).…”

Section: Downloaded Frommentioning

confidence: 99%

Altered eicosanoid production and phospholipid remodeling during cell culture

Okuno

Gijón

Zarini

et al. 2018

Journal of Lipid Research

View full text Add to dashboard Cite

“…It has also been shown that in mouse embryonic fibroblasts and NIH 3T3 cells 18:0/20:4 PI species were the most abundant . More recent information using improved methodology confirms these findings and concludes that 50–80% of PI/PIPn have 18:0/20:4 acyl chains ( Figure ) …”

Section: Pi/pipn Acyl Chain Profile In Mammalsmentioning

confidence: 78%

“…Some phospholipids present predominant acyl chains in a tissue‐specific manner; for instance, in mammalian heart cardiolipin has predominantly four linoleoyl (18:2) acyl chains . However, PI 18:0/20:4 acyl chain enrichment seems ubiquitous to the whole organism in mammals, with the exception of lamb liver . The presence of PI enriched with specific acyl chains has been shown to be present across taxonomy; although, the specific molecular species varies …”

Section: Pi/pipn Acyl Chain Profile In Mammalsmentioning

confidence: 99%

“…However, contrary to the majority of the other glycerophospholipids PI/PIPn are highly enriched with specific acyl chains. In mammals, the predominant molecular species of PI/PIPn is 1‐stearoyl‐2‐arachidonoyl‐PI (SAPI; 18:0/20:4‐PI—the X : Y numeric identification of the acyl chains refers to the number of carbon atoms and double bonds, respectively) . Herein we will review the i) PI/PIPn acyl chain profile in mammals; ii) circumstances with altered PI/PIPn acyl chain profile; iii) the molecular mechanisms that lead to this acyl chain enrichment; iv) physiological implications of altered PI/PIPn acyl chain profile; and v) the putative functional role of these specific acyl chains.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Specificity of Acyl Chain Composition of Phosphatidylinositols

Bozelli

Epand

2019

Proteomics

View full text Add to dashboard Cite

Phosphatidylinositol (PI) lipids have a predominance of a single molecular species present through the organism. In healthy mammals this molecular species is 1‐stearoyl‐2‐arachidonoyl (18:0/20:4) PI. Although the importance of PI lipids for cell physiology has long been appreciated, less is known about the biological role of enriching PI lipids with 18:0/20:4 acyl chains. In conditions with dysfunctional lipid metabolism, the predominance of 18:0/20:4 acyl chains is lost. Recently, molecular mechanisms underpinning the enrichment or alteration of these acyl chains in PI lipids have begun to emerge. In the majority of the cases a common feature is the presence of enzymes bearing substrate acyl chain specificity. However, in cancer cells, it has been shown that one (not the only) of the mechanisms responsible for the loss in this acyl chain enrichment is mutation on the transcription factor p53 gene, which is one of the most highly mutated genes in cancers. There is a compelling need for a global picture of the specificity of the acyl chain composition of PIs. This can be possible once high‐resolution spatio‐temporal information is gathered in a cellular context; which can ultimately lead to potential novel targets to combat conditions with altered PI acyl chain profiles.

show abstract

Fatty-acyl chain profiles of cellular phosphoinositides

Cited by 92 publications

References 64 publications

Muscarinic receptor regulates extracellular signal regulated kinase by two modes of arrestin binding

Muscarinic receptor regulates extracellular signal regulated kinase by two modes of arrestin binding

Altered eicosanoid production and phospholipid remodeling during cell culture

Specificity of Acyl Chain Composition of Phosphatidylinositols

Contact Info

Product

Resources

About