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Biochimica Et Biophysica Acta Sep 2016Phosphoinositides and soluble inositol phosphates are essential components of a complex intracellular chemical code that regulates major aspects of lipid signaling in... (Review)
Review
Phosphoinositides and soluble inositol phosphates are essential components of a complex intracellular chemical code that regulates major aspects of lipid signaling in eukaryotes. These involvements span a broad array of biological outcomes and activities, and cells are faced with the problem of how to compartmentalize and organize these various signaling events into a coherent scheme. It is in the arena of how phosphoinositide signaling circuits are integrated and, and how phosphoinositide pools are functionally defined and channeled to privileged effectors, that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as critical players. As plant systems offer some unique advantages and opportunities for study of these proteins, we discuss herein our perspectives regarding the progress made in plant systems regarding PITP function. We also suggest interesting prospects that plant systems hold for interrogating how PITPs work, particularly in multi-domain contexts, to diversify the biological outcomes for phosphoinositide signaling. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner.
Topics: Lipid Metabolism; Phosphatidylinositol Phosphates; Phosphatidylinositols; Phospholipid Transfer Proteins; Plants; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction
PubMed: 27038688
DOI: 10.1016/j.bbalip.2016.03.027 -
The Journal of Biological Chemistry 2021Ceramide-1-phosphate transfer proteins (CPTPs) are members of the glycolipid transfer protein (GLTP) superfamily that shuttle ceramide-1-phosphate (C1P) between...
Ceramide-1-phosphate transfer proteins (CPTPs) are members of the glycolipid transfer protein (GLTP) superfamily that shuttle ceramide-1-phosphate (C1P) between membranes. CPTPs regulate cellular sphingolipid homeostasis in ways that impact programmed cell death and inflammation. CPTP downregulation specifically alters C1P levels in the plasma and trans-Golgi membranes, stimulating proinflammatory eicosanoid production and autophagy-dependent inflammasome-mediated cytokine release. However, the mechanisms used by CPTP to target the trans-Golgi and plasma membrane are not well understood. Here, we monitored C1P intervesicular transfer using fluorescence energy transfer (FRET) and showed that certain phosphoinositides (phosphatidylinositol 4,5 bisphosphate (PI-(4,5)P) and phosphatidylinositol 4-phosphate (PI-4P)) increased CPTP transfer activity, whereas others (phosphatidylinositol 3-phosphate (PI-3P) and PI) did not. PIPs that stimulated CPTP did not stimulate GLTP, another superfamily member. Short-chain PI-(4,5)P which is soluble and does not remain membrane-embedded, failed to activate CPTP. CPTP stimulation by physiologically relevant PI-(4,5)P levels surpassed that of phosphatidylserine (PS), the only known non-PIP stimulator of CPTP, despite PI-(4,5)P increasing membrane equilibrium binding affinity less effectively than PS. Functional mapping of mutations that led to altered FRET lipid transfer and assessment of CPTP membrane interaction by surface plasmon resonance indicated that di-arginine motifs located in the α-6 helix and the α3-α4 helix regulatory loop of the membrane-interaction region serve as PI-(4,5)P headgroup-specific interaction sites. Haddock modeling revealed specific interactions involving the PI-(4,5)P headgroup that left the acyl chains oriented favorably for membrane embedding. We propose that PI-(4,5)P interaction sites enhance CPTP activity by serving as preferred membrane targeting/docking sites that favorably orient the protein for function.
Topics: Homeostasis; Humans; Models, Molecular; Phosphatidylinositols; Phospholipid Transfer Proteins; Protein Conformation, alpha-Helical
PubMed: 33781749
DOI: 10.1016/j.jbc.2021.100600 -
Biochimica Et Biophysica Acta.... Feb 2020Epithelial cells are polarized cells and typically display distinct plasma membrane domains: basal plasma membrane domains face the underlying tissue, lateral domains... (Review)
Review
Epithelial cells are polarized cells and typically display distinct plasma membrane domains: basal plasma membrane domains face the underlying tissue, lateral domains contact adjacent cells and apical domains face the exterior lumen. Each membrane domain is endowed with a specific macromolecular composition that constitutes the functional identity of that domain. Defects in apical-basal plasma membrane polarity altogether or more subtle defects in the composition of either apical or basal plasma membrane domain can give rise to severe diseases. Lipids are the main component of cellular membranes and mechanisms that control their polarized distribution in epithelial cells are emerging. In particular sphingolipids and phosphatidylinositol lipids have taken center stage in the organization of the apical and basolateral plasma membrane domain. This short review article discusses mechanisms that contribute to the polarized distribution of lipids in epithelial cells.
Topics: Animals; Cell Polarity; Endosomes; Epithelial Cells; Humans; Phosphatidylinositols
PubMed: 31809710
DOI: 10.1016/j.bbamem.2019.183145 -
Journal of Biochemistry Oct 2020Inositol phospholipids are low-abundance regulatory lipids that orchestrate diverse cellular functions in eukaryotic organisms. Recent studies have uncovered involvement... (Review)
Review
Inositol phospholipids are low-abundance regulatory lipids that orchestrate diverse cellular functions in eukaryotic organisms. Recent studies have uncovered involvement of the lipids in multiple steps in autophagy. The late endosome-lysosome compartment plays critical roles in cellular nutrient sensing and in the control of both the initiation of autophagy and the late stage of eventual degradation of cytosolic materials destined for elimination. It is particularly notable that inositol lipids are involved in almost all steps of the autophagic process. In this review, we summarize how inositol lipids regulate and contribute to autophagy through the endomembrane compartments, primarily focusing on PI4P and PI(4,5)P2.
Topics: Animals; Autophagy; Endosomes; Humans; Lysosomes; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phosphatidylinositols; Signal Transduction
PubMed: 32745205
DOI: 10.1093/jb/mvaa089 -
Pflugers Archiv : European Journal of... Sep 2015The heat- and capsaicin-sensitive transient receptor potential vanilloid 1 ion channel (TRPV1) is regulated by plasma membrane phosphoinositides. The effects of these... (Review)
Review
The heat- and capsaicin-sensitive transient receptor potential vanilloid 1 ion channel (TRPV1) is regulated by plasma membrane phosphoinositides. The effects of these lipids on this channel have been controversial. Recent articles re-ignited the debate and also offered resolution to place some of the data in a coherent picture. This review summarizes the literature on this topic and provides a detailed and critical discussion on the experimental evidence for the various effects of phosphatidylinositol 4,5-bisphosphayte [PI(4,5)P2 or PIP2] on TRPV1. We conclude that PI(4,5)P2 and potentially its precursor PI(4)P are positive cofactors for TRPV1, acting via direct interaction with the channel, and their depletion by Ca(2+)-induced activation of phospholipase Cδ isoforms (PLCδ) limits channel activity during capsaicin-induced desensitization. Other negatively charged lipids at higher concentrations can also support channel activity, which may explain some controversies in the literature. PI(4,5)P2 also partially inhibits channel activity in some experimental settings, and relief from this inhibition upon PLCβ activation may contribute to sensitization. The negative effect of PI(4,5)P2 is more controversial and its mechanism is less well understood. Other TRP channels from the TRPV and TRPC families may also undergo similar dual regulation by phosphoinositides, thus the complexity of TRPV1 regulation is not unique to this channel.
Topics: Animals; Humans; Phosphatidylinositols; TRPV Cation Channels
PubMed: 25754030
DOI: 10.1007/s00424-015-1695-3 -
Physiological Reviews Jul 2004Proteins that make, consume, and bind to phosphoinositides are important for constitutive membrane traffic. Different phosphoinositides are concentrated in different... (Review)
Review
Proteins that make, consume, and bind to phosphoinositides are important for constitutive membrane traffic. Different phosphoinositides are concentrated in different parts of the central vacuolar pathway, with phosphatidylinositol 4-phosphate predominate on Golgi, phosphatidylinositol 4,5-bisphosphate predominate at the plasma membrane, phosphatidylinositol 3-phosphate the major phosphoinositide on early endosomes, and phosphatidylinositol 3,5-bisphosphate found on late endocytic organelles. This spatial segregation may be the mechanism by which the direction of membrane traffic is controlled. Phosphoinositides increase the affinity of membranes for peripheral membrane proteins that function for sorting protein cargo or for the docking and fusion of transport vesicles. This implies that constitutive membrane traffic may be regulated by the mechanisms that control the activity of the enzymes that produce and consume phosphoinositides. Although the lipid kinases and phosphatases that function in constitutive membrane traffic are beginning to be identified, their regulation is poorly understood.
Topics: Animals; Carrier Proteins; Humans; Intracellular Membranes; Phosphatidylinositols; Phosphoric Monoester Hydrolases; Phosphotransferases; Tissue Distribution
PubMed: 15269334
DOI: 10.1152/physrev.00033.2003 -
The Journal of Cell Biology Aug 2023The maintenance of plasma membrane integrity and a capacity for efficiently repairing damaged membranes are essential for cell survival. Large-scale wounding depletes...
The maintenance of plasma membrane integrity and a capacity for efficiently repairing damaged membranes are essential for cell survival. Large-scale wounding depletes various membrane components at the wound sites, including phosphatidylinositols, yet little is known about how phosphatidylinositols are generated after depletion. Here, working with our in vivo C. elegans epidermal cell wounding model, we discovered phosphatidylinositol 4-phosphate (PtdIns4P) accumulation and local phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] generation at the wound site. We found that PtdIns(4,5)P2 generation depends on the delivery of PtdIns4P, PI4K, and PI4P 5-kinase PPK-1. In addition, we show that wounding triggers enrichment of the Golgi membrane to the wound site, and that is required for membrane repair. Moreover, genetic and pharmacological inhibitor experiments support that the Golgi membrane provides the PtdIns4P for PtdIns(4,5)P2 generation at the wounds. Our findings demonstrate how the Golgi apparatus facilitates membrane repair in response to wounding and offers a valuable perspective on cellular survival mechanisms upon mechanical stress in a physiological context.
Topics: Animals; Caenorhabditis elegans; Cell Membrane; Golgi Apparatus; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Stress, Mechanical
PubMed: 37158801
DOI: 10.1083/jcb.202303017 -
FEBS Letters Aug 2016Phosphoinositides represent a very small fraction of membrane phospholipids, having fast turnover rates and unique subcellular distributions, which make them perfect for... (Review)
Review
Phosphoinositides represent a very small fraction of membrane phospholipids, having fast turnover rates and unique subcellular distributions, which make them perfect for initiating local temporal effects. Seven different phosphoinositide species are generated through reversible phosphorylation of the inositol ring of phosphatidylinositol (PtdIns). The negative charge generated by the phosphates provides specificity for interaction with various protein domains that commonly contain a cluster of basic residues. Examples of domains that bind phosphoinositides include PH domains, WD40 repeats, PX domains, and FYVE domains. Such domains often display specificity toward a certain species or subset of phosphoinositides. Here we will review the current literature of different phosphoinositide-binding proteins involved in autophagy.
Topics: Autophagy; Binding Sites; Phosphatidylinositols; Phosphorylation; Protein Binding; Protein Domains; Proteins; Repetitive Sequences, Amino Acid
PubMed: 27391591
DOI: 10.1002/1873-3468.12286 -
The Biochemical Journal Nov 2022In the almost 70 years since the first hints of its existence, the phosphoinositide, phosphatidyl-D-myo-inositol 4,5-bisphosphate has been found to be central in the...
In the almost 70 years since the first hints of its existence, the phosphoinositide, phosphatidyl-D-myo-inositol 4,5-bisphosphate has been found to be central in the biological regulation of plasma membrane (PM) function. Here, we provide an overview of the signaling, transport and structural roles the lipid plays at the cell surface in animal cells. These include being substrate for second messenger generation, direct modulation of receptors, control of membrane traffic, regulation of ion channels and transporters, and modulation of the cytoskeleton and cell polarity. We conclude by re-evaluating PI(4,5)P2's designation as a signaling molecule, instead proposing a cofactor role, enabling PM-selective function for many proteins.
Topics: Animals; Cell Membrane; Phosphatidylinositols; Signal Transduction; Ion Channels; Phosphatidylinositol 4,5-Diphosphate
PubMed: 36367756
DOI: 10.1042/BCJ20220445 -
Nature Communications Jan 2022Phosphoinositides are a family of membrane lipids essential for many biological and pathological processes. Due to the existence of multiple phosphoinositide...
Phosphoinositides are a family of membrane lipids essential for many biological and pathological processes. Due to the existence of multiple phosphoinositide regioisomers and their low intracellular concentrations, profiling these lipids and linking a specific acyl variant to a change in biological state have been difficult. To enable the comprehensive analysis of phosphoinositide phosphorylation status and acyl chain identity, we develop PRMC-MS (Phosphoinositide Regioisomer Measurement by Chiral column chromatography and Mass Spectrometry). Using this method, we reveal a severe skewing in acyl chains in phosphoinositides in Pten-deficient prostate cancer tissues, extracellular mobilization of phosphoinositides upon expression of oncogenic PIK3CA, and a unique profile for exosomal phosphoinositides. Thus, our approach allows characterizing the dynamics of phosphoinositide acyl variants in intracellular and extracellular milieus.
Topics: Animals; Chromatography, Affinity; Class I Phosphatidylinositol 3-Kinases; Epidermal Growth Factor; Exosomes; Gene Expression; HEK293 Cells; HeLa Cells; Humans; Male; Mass Spectrometry; Metabolome; Mice; PC-3 Cells; PTEN Phosphohydrolase; Phosphatidylinositols; Prostate; Prostatic Neoplasms; Pyrimidines; Quinazolines; Stereoisomerism
PubMed: 35013169
DOI: 10.1038/s41467-021-27648-z