-
Biochimica Et Biophysica Acta.... Nov 2017Phosphatidyl-myo-inositol mannosides (PIMs) are glycolipids of unique chemical structure found in the inner and outer membranes of the cell envelope of all Mycobacterium... (Review)
Review
Phosphatidyl-myo-inositol mannosides (PIMs) are glycolipids of unique chemical structure found in the inner and outer membranes of the cell envelope of all Mycobacterium species. The PIM family of glycolipids comprises phosphatidyl-myo-inositol mono-, di-, tri-, tetra-, penta-, and hexamannosides with different degrees of acylation. PIMs are considered not only essential structural components of the cell envelope but also the precursors of lipomannan and lipoarabinomannan, two major lipoglycans implicated in host-pathogen interactions. Since the description of the complete chemical structure of PIMs, major efforts have been committed to defining the molecular bases of its biosynthetic pathway. The structural characterization of the integral membrane phosphatidyl-myo-inositol phosphate synthase (PIPS), and that of three enzymes working at the protein-membrane interface, the phosphatidyl-myo-inositol mannosyltransferases A and B, and the acyltransferase PatA, established the basis of the early steps of the PIM pathway at the molecular level. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.
Topics: Acyltransferases; Bacterial Proteins; Cell Wall; Glycosyltransferases; Lipogenesis; Mannosyltransferases; Models, Molecular; Mycobacterium; Phosphatidylinositols; Protein Conformation; Structure-Activity Relationship; Transferases (Other Substituted Phosphate Groups)
PubMed: 27826050
DOI: 10.1016/j.bbalip.2016.11.002 -
Antiviral Research May 2023Phosphatidylinositol lipids play vital roles in lipid signal transduction, membrane recognition, vesicle transport, and viral replication. Previous studies have revealed...
Phosphatidylinositol lipids play vital roles in lipid signal transduction, membrane recognition, vesicle transport, and viral replication. Previous studies have revealed that SAC1-like phosphatidylinositol phosphatase (SACM1L/SAC1), which uses phosphatidylinositol-4-phosphate (PI4P) as its substrate, greatly affects the replication of certain bacteria and viruses in vitro. However, it remains unclear whether and how SAC1 modulates hepatitis B virus (HBV) replication in vitro and in vivo. In the present study, we observed that SAC1 silencing significantly increased HBV DNA replication, subviral particle (SVP) expression, and secretion of HBV virions, whereas SAC1 overexpression exerted the opposite effects. Moreover, SAC1 overexpression inhibited HBV DNA replication and SVP expression in a hydrodynamic injection-based HBV-persistent replicating mouse model. Mechanistically, SAC1 silencing increased the number of HBV-containing autophagosomes as well as PI4P levels on the autophagosome membrane. Moreover, SAC1 silencing blocked autophagosome-lysosome fusion by inhibiting the interaction between synaptosomal-associated protein 29 and vesicle-associated membrane protein 8. Collectively, our data indicate that SAC1 significantly inhibits HBV replication by promoting the autophagic degradation of HBV virions. Our findings support that SAC1-mediated phospholipid metabolism greatly modulates certain steps of the HBV life-cycle and provide a new theoretical basis for antiviral therapy.
Topics: Animals; Mice; Hepatitis B virus; Virus Replication; Hepatitis B; Phosphatidylinositols; Virion; Phosphoric Monoester Hydrolases
PubMed: 37068596
DOI: 10.1016/j.antiviral.2023.105601 -
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 -
Biochimica Et Biophysica Acta.... Mar 2022Phosphoinositides are a family of signaling lipids that play a profound role in regulating protein function at the membrane-cytosol interface of all cellular membranes.... (Review)
Review
Phosphoinositides are a family of signaling lipids that play a profound role in regulating protein function at the membrane-cytosol interface of all cellular membranes. Underscoring their importance, mutations or alterations in phosphoinositide metabolizing enzymes lead to host of developmental, neurodegenerative, and metabolic disorders that are devastating for human health. In addition to lipid enzymes, phosphoinositide metabolism is regulated and controlled at membrane contact sites (MCS). Regions of close opposition typically between the ER and other cellular membranes, MCS are non-vesicular lipid transport portals that engage in extensive communication to influence organelle homeostasis. This review focuses on lipid transport, specifically phosphoinositide lipid transport and metabolism at MCS.
Topics: Phosphatidylinositols
PubMed: 34995791
DOI: 10.1016/j.bbalip.2021.159107 -
Biochimica Et Biophysica Acta Sep 2016Eukaryotic membranes contain small amounts of lipids with regulatory roles. An important class of such regulatory lipids are phosphoinositides (PIs). Within membranes,... (Review)
Review
Eukaryotic membranes contain small amounts of lipids with regulatory roles. An important class of such regulatory lipids are phosphoinositides (PIs). Within membranes, PIs serve as recruitment signals, as regulators of membrane protein function or as precursors for second messenger production, thereby influencing a multitude of cellular processes with key importance for plant function and development. Plant PIs occur locally and transiently within membrane microdomains, and their abundance is strictly controlled. To understand the functions of the plant PI-network it is important to understand not only downstream PI-effects, but also to identify and characterize factors contributing to dynamic PI formation. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner.
Topics: Lipids; Membrane Proteins; Phosphatidylinositols; Plants; Second Messenger Systems; Signal Transduction
PubMed: 26924252
DOI: 10.1016/j.bbalip.2016.02.013 -
Advances in Biological Regulation Jan 2023Aberrant signaling pathways regulating proliferation and differentiation of hematopoietic stem cells (HSCs) can contribute to disease pathogenesis and neoplastic growth....
Aberrant signaling pathways regulating proliferation and differentiation of hematopoietic stem cells (HSCs) can contribute to disease pathogenesis and neoplastic growth. Phosphoinositides (PIs) are inositol phospholipids that are implicated in the regulation of critical signaling pathways: aberrant regulation of Phospholipase C (PLC) beta1, PLCgamma1 and the PI3K/Akt/mTOR pathway play essential roles in the pathogenesis of Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML).
Topics: Humans; Phosphatidylinositol 3-Kinases; Signal Transduction; Leukemia, Myeloid, Acute; Phosphatidylinositols; Myelodysplastic Syndromes
PubMed: 36706610
DOI: 10.1016/j.jbior.2023.100955 -
Advances in Biological Regulation Jan 2016Phosphatidylinositol 4,5-bisphosphate (PI4,5P2) is a lipid messenger that regulates a wide variety of cellular functions. The majority of cellular PI4,5P2 is generated... (Review)
Review
Phosphatidylinositol 4,5-bisphosphate (PI4,5P2) is a lipid messenger that regulates a wide variety of cellular functions. The majority of cellular PI4,5P2 is generated by isoforms of the type I phosphatidylinositol phosphate kinases (PIPKI) that are generated from three genes, and each PIPKI isoform has a unique distribution and function in cells. It has been shown that the signaling specificity of PI4,5P2 can be determined by a physical association of PIPKs with PI4,5P2 effectors. IQGAP1 is newly identified as an interactor of multiple isoforms of PIPKs. Considering the versatile roles of IQGAP1 in cellular signaling pathways, IQGAP1 may confer isoform-specific roles of PIPKs in distinct cellular locations. In this mini review, the emerging roles of PIPKs that are regulated by an association with IQGAP1 will be summarized. Focuses will be on cell migration, vesicle trafficking, cell signaling, and nuclear events.
Topics: Animals; Humans; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Phosphotransferases (Alcohol Group Acceptor); Protein Binding; Signal Transduction; ras GTPase-Activating Proteins
PubMed: 26554303
DOI: 10.1016/j.jbior.2015.10.004 -
Archives of Pharmacal Research Aug 2016Autophagy is an evolutionarily conserved cellular process for lysosomal degradation, which is involved in various physiological processes within cells. Its dysfunction... (Review)
Review
Autophagy is an evolutionarily conserved cellular process for lysosomal degradation, which is involved in various physiological processes within cells. Its dysfunction is associated with many human diseases, such as cancer, liver diseases, heart diseases, and infectious diseases, including neurodegenerative diseases. Autophagy involves the formation of a double-membrane bound autophagosome and the degradation of cytosolic components via its fusion and maturation with the lysosome. One of the most important steps in the process of autophagy is membrane biogenesis during autophagosome formation/maturation from different membrane sources within cells. However, there is limited knowledge regarding: (1) how the core autophagy machinery is recruited to the initial site to initiate the formation of the isolation membrane and (2) how the autophagosome matures into the functional autolysosome. Lipid supply for nucleation/elongation of the autophagosome has been proposed as one possible mechanism. Accumulating evidence suggests the important role of phosphoinositides as phospholipids, which represent key membrane-localized signals in the regulation of fundamental cellular processes, in autophagosome formation and maturation. This review focuses on how phosphoinositides influence autophagy induction or autophagosome biogenesis/maturation, because the way they are altered by autophagy might contribute to the pathogenesis of human diseases.
Topics: Animals; Autophagosomes; Autophagy; Humans; Phosphatidylinositols
PubMed: 27350551
DOI: 10.1007/s12272-016-0777-x -
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 -
The Journal of Cell Biology Sep 2023The lipid phosphatidylinositol 3,5-bisphosphate-PI(3,5)P2-is known to be a key regulator of cellular traffic in health and disease, but its cellular localization was...
The lipid phosphatidylinositol 3,5-bisphosphate-PI(3,5)P2-is known to be a key regulator of cellular traffic in health and disease, but its cellular localization was somewhat enigmatic until now, with the discovery of a new PI(3,5)P2 biosensor reported in this issue of JCB by Vines et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202209077).
Topics: Phosphatidylinositol Phosphates; Phosphatidylinositols; Biosensing Techniques
PubMed: 37578524
DOI: 10.1083/jcb.202308004