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International Journal of Biological... 2020Phosphoinositides are membrane lipids generated by phosphorylation on the inositol head group of phosphatidylinositol. By specifically distributed to distinct... (Review)
Review
Phosphoinositides are membrane lipids generated by phosphorylation on the inositol head group of phosphatidylinositol. By specifically distributed to distinct subcellular membrane locations, different phosphoinositide species play diverse roles in modulating membrane trafficking. Among the seven known phosphoinositide species, phosphatidylinositol 4,5-bisphosphate (PI4,5P) is the one species most abundant at the plasma membrane. Thus, the PI4,5P function in membrane trafficking is first identified in controlling plasma membrane dynamic-related events including endocytosis and exocytosis. However, recent studies indicate that PI4,5P is also critical in many other membrane trafficking events such as endosomal trafficking, hydrolases sorting to lysosomes, autophagy initiation, and autophagic lysosome reformation. These findings suggest that the role of PI4,5P in membrane trafficking is far beyond just plasma membrane. This review will provide a concise synopsis of how PI4,5P functions in multiple membrane trafficking events. PI4,5P, the enzymes responsible for PI4,5P production at specific subcellular locations, and distinct PI4,5P effector proteins compose a regulation network to control the specific membrane trafficking events.
Topics: Cell Membrane; Cell Movement; Endocytosis; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols
PubMed: 33061794
DOI: 10.7150/ijbs.49665 -
The New Phytologist Aug 2022Phosphatidylinositol 4-phosphate (PI4P) is an anionic phospholipid which has been described as a master regulator of the Golgi apparatus in eukaryotic cells. However,... (Review)
Review
Phosphatidylinositol 4-phosphate (PI4P) is an anionic phospholipid which has been described as a master regulator of the Golgi apparatus in eukaryotic cells. However, recent evidence suggests that PI4P mainly accumulates at the plasma membrane in all plant cells analyzed so far. In addition, many functions that are typically attributed to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P ) in animal and yeast cells are also supported by PI4P in plants. For example, PI4P is the key anionic lipid that powers the strong electrostatic properties of the plasma membrane. Phosphatidylinositol 4-phosphate is also required for the establishment of stable membrane contacts between the endoplasmic reticulum and the plasma membrane, for exocytosis and to support signaling pathways. Thus, we propose that PI4P has a prominent role in specifying the identity of the plasma membrane and in supporting some of its key functions and should be considered a hallmark lipid of this compartment.
Topics: Animals; Cell Membrane; Golgi Apparatus; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phosphatidylinositols
PubMed: 35586972
DOI: 10.1111/nph.18258 -
Biochemical Pharmacology Feb 2024Phosphatidylinositol 4-kinases (PI4Ks) could phosphorylate phosphatidylinositol (PI) to produce phosphatidylinositol 4-phosphate (PI4P) and maintain its metabolic... (Review)
Review
Phosphatidylinositol 4-kinases (PI4Ks) could phosphorylate phosphatidylinositol (PI) to produce phosphatidylinositol 4-phosphate (PI4P) and maintain its metabolic balance and location. PI4P, the most abundant monophosphate inositol in eukaryotic cells, is a precursor of higher phosphoinositols and an essential substrate for the PLC/PKC and PI3K/Akt signaling pathways. PI4Ks regulate vesicle transport, signal transduction, cytokinesis, and cell unity, and are involved in various physiological and pathological processes, including infection and growth of parasites such as Plasmodium and Cryptosporidium, replication and survival of RNA viruses, and the development of tumors and nervous system diseases. The development of novel drugs targeting PI4Ks and PI4P has been the focus of the research and clinical application of drugs, especially in recent years. In particular, PI4K inhibitors have made great progress in the treatment of malaria and cryptosporidiosis. We describe the biological characteristics of PI4Ks; summarize the physiological functions and effector proteins of PI4P; and analyze the structural basis of selective PI4K inhibitors for the treatment of human diseases in this review. Herein, this review mainly summarizes the developments in the structure and enzyme activity of PI4K inhibitors.
Topics: Humans; 1-Phosphatidylinositol 4-Kinase; Phosphatidylinositol 3-Kinases; Cryptosporidiosis; Cryptosporidium; Phosphatidylinositol Phosphates; Phosphatidylinositols
PubMed: 38151075
DOI: 10.1016/j.bcp.2023.115993 -
The Biochemical Journal Mar 2009Membrane fusion underlies many cellular events, including secretion, exocytosis, endocytosis, organelle reconstitution, transport from endoplasmic reticulum to Golgi and... (Review)
Review
Membrane fusion underlies many cellular events, including secretion, exocytosis, endocytosis, organelle reconstitution, transport from endoplasmic reticulum to Golgi and nuclear envelope formation. A large number of investigations into membrane fusion indicate various roles for individual members of the phosphoinositide class of membrane lipids. We first review the phosphoinositides as membrane recognition sites and their regulatory functions in membrane fusion. We then consider how modulation of phosphoinositides and their products may affect the structure and dynamics of natural membranes facilitating fusion. These diverse roles underscore the importance of these phospholipids in the fusion of biological membranes.
Topics: Animals; Cell Membrane; Humans; Lipid Metabolism; Membrane Fusion; Membrane Lipids; Membrane Proteins; Metabolic Networks and Pathways; Models, Biological; Phosphatidylinositols
PubMed: 19196244
DOI: 10.1042/BJ20082105 -
Biochemical Society Transactions Jun 2006Yeast Sec14p acts as a phosphatidylinositol/phosphatidylcholine-transfer protein in vitro. In vivo, it is essential in promoting Golgi secretory function. Products of... (Review)
Review
Yeast Sec14p acts as a phosphatidylinositol/phosphatidylcholine-transfer protein in vitro. In vivo, it is essential in promoting Golgi secretory function. Products of five genes named SFH1-SFH5 (Sec Fourteen Homologues 1-5) exhibit significant sequence homology to Sec14p and together they form the Sec14p family of lipid-transfer proteins. It is a diverse group of proteins with distinct subcellular localizations and varied physiological functions related to lipid metabolism and membrane trafficking.
Topics: Multigene Family; Phosphatidylinositols; Phospholipid Transfer Proteins; Saccharomyces cerevisiae; Sequence Homology, Amino Acid
PubMed: 16709166
DOI: 10.1042/BST0340377 -
Traffic (Copenhagen, Denmark) Feb 2020Among the structural phospholipids that form the bulk of eukaryotic cell membranes, phosphatidylinositol (PtdIns) is unique in that it also serves as the common... (Review)
Review
Among the structural phospholipids that form the bulk of eukaryotic cell membranes, phosphatidylinositol (PtdIns) is unique in that it also serves as the common precursor for low-abundance regulatory lipids, collectively referred to as polyphosphoinositides (PPIn). The metabolic turnover of PPIn species has received immense attention because of the essential functions of these lipids as universal regulators of membrane biology and their dysregulation in numerous human pathologies. The diverse functions of PPIn lipids occur, in part, by orchestrating the spatial organization and conformational dynamics of peripheral or integral membrane proteins within defined subcellular compartments. The emerging role of stable contact sites between adjacent membranes as specialized platforms for the coordinate control of ion exchange, cytoskeletal dynamics, and lipid transport has also revealed important new roles for PPIn species. In this review, we highlight the importance of membrane contact sites formed between the endoplasmic reticulum (ER) and plasma membrane (PM) for the integrated regulation of PPIn metabolism within the PM. Special emphasis will be placed on non-vesicular lipid transport during control of the PtdIns biosynthetic cycle as well as toward balancing the turnover of the signaling PPIn species that define PM identity.
Topics: Biological Transport; Cell Membrane; Endoplasmic Reticulum; Humans; Phosphatidylinositol Phosphates; Phosphatidylinositols
PubMed: 31650663
DOI: 10.1111/tra.12709 -
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 -
Methods in Molecular Biology (Clifton,... 2021Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) is an enzyme that converts phosphatidylinositol 4-phosphate [PI4P] to phosphatidylinositol 4,5-bisphosphate [PI(4,5)P]....
Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) is an enzyme that converts phosphatidylinositol 4-phosphate [PI4P] to phosphatidylinositol 4,5-bisphosphate [PI(4,5)P]. PIP5K plays a key role in the regulation of vesicular transport, cytoskeleton reorganization, and cell division. In general, to investigate an enzymatic activity of PIP5K, the amount of incorporated [P] ATP into PI(4,5)P fraction is measured in in vitro reconstitution experiments. However, tools to monitor dynamic changes in its activity in real time have been lacking. Recently, we have developed a novel PIP5K assay using fluorescence spectroscopy. Compared to conventional methods in which lipids extraction steps are needed, our method is easy and quick to perform and enables a real-time analysis. This chapter provides a protocol to set up and perform the novel PIP5K assay we have recently established.
Topics: Animals; Humans; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phosphatidylinositols; Phosphotransferases (Alcohol Group Acceptor); Protein Transport; Spectrometry, Fluorescence
PubMed: 33481235
DOI: 10.1007/978-1-0716-1142-5_8 -
FASEB Journal : Official Publication of... Mar 1989Covalent linkage of proteins to glycosyl-phosphatidylinositol (GPI) molecules is now recognized as an important mechanism for anchoring proteins to membranes. Recent... (Review)
Review
Covalent linkage of proteins to glycosyl-phosphatidylinositol (GPI) molecules is now recognized as an important mechanism for anchoring proteins to membranes. Recent structural work on the GPI anchors indicates that the structure of the glycan connecting the protein and the phosphatidylinositol molecule has been conserved during evolution. Attachment of the protein to the GPI molecule is directed by a signal sequence at the COOH terminus of the polypeptide that is removed during the attachment process. Alternative processing of the same RNA transcript may lead to mRNA species encoding for the same protein but not utilizing GPI for membrane anchoring. One function of the GPI anchor may be to offer a site for degradation by specific endogenous phospholipases with release of the protein from the cell surface. The products of GPI anchor degradation may also have biological activity and be involved in cell communication. Although the physiological role of these events is not certain, the available evidence suggests that the GPI anchors play a dynamic and versatile role in the regulation of cell surface protein expression.
Topics: Animals; Biological Evolution; Cell Communication; Gene Expression Regulation; Glycolipids; Glycosylphosphatidylinositols; Humans; Membrane Proteins; Molecular Structure; Phosphatidylinositols; Protein Sorting Signals
PubMed: 2522071
DOI: 10.1096/fasebj.3.5.2522071 -
Cell Nov 1990Studies of phosphatidylinositol signaling pathways are entering a new phase in which molecular genetic techniques are providing powerful tools to dissect the functions... (Review)
Review
Studies of phosphatidylinositol signaling pathways are entering a new phase in which molecular genetic techniques are providing powerful tools to dissect the functions of various metabolites and pathways. Studies with phospholipase C are most advanced and clearly indicate that phosphatidylinositol turnover is critical for vision in Drosophila and cell proliferation in various cultured cells. Expression of cDNA constructs and microinjection of PLC or antibodies against it clearly establish a role for PtdIns signaling distinct from its role in calcium mobilization and protein kinase C activation. The importance of inositol cyclic phosphates is also beginning to be realized from the study of cyclic hydrolase using similar techniques. Elucidation of the function of the 3-phosphate inositol phospholipid pathway awaits similar studies. The recent cDNA cloning of inositol monophosphatase (Diehl et al., 1990), Ins(1,4,5)P3 3-kinase (Choi et al., 1990), and inositol polyphosphate 1-phosphatase (York and Majerus, 1991) should provide tools to define further the cell biology of the phosphatidylinositol signaling pathway.
Topics: Animals; Models, Biological; Phosphatidylinositols; Signal Transduction; Type C Phospholipases
PubMed: 2225061
DOI: 10.1016/0092-8674(90)90442-h