A5103004242- Lipid metabolism and biosynthesis
- Fungal and yeast genetics research
- Endoplasmic Reticulum Stress and Disease
- Microbial Metabolic Engineering and Bioproduction
- Cellular transport and secretion
- Protein Structure and Dynamics
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Enzyme Catalysis and Immobilization
- Photosynthetic Processes and Mechanisms
- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Research in Cotton Cultivation
- Microtubule and mitosis dynamics
- Plant biochemistry and biosynthesis
- Adipose Tissue and Metabolism
- Trace Elements in Health
- Pancreatic function and diabetes
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
- Mass Spectrometry Techniques and Applications
- Autophagy in Disease and Therapy
- Cancer, Hypoxia, and Metabolism
Rutgers, The State University of New Jersey
2016-2025
Rutgers Sexual and Reproductive Health and Rights
2006-2024
The University of Texas Health Science Center at Houston
2024
Rütgers (Germany)
2024
Universitätsklinikum des Saarlandes
2011
Phosphorylation of the conserved lipin Pah1p/Smp2p in Saccharomyces cerevisiae was previously shown to control transcription phospholipid biosynthetic genes and nuclear structure by regulating amount membrane present at envelope (Santos-Rosa, H., Leung, J., Grimsey, N., Peak-Chew, S., Siniossoglou, S. (2005) EMBO J. 24, 1931-1941). A recent report identified Pah1p as a Mg2+-dependent phosphatidate (PA) phosphatase that regulates de novo lipid synthesis (Han G.-S., Wu, W. I., Carman, G. M....
Regulation of membrane lipid composition is crucial for many aspects cell growth and development. Lipins, a novel family phosphatidate (PA) phosphatases that generate diacylglycerol (DAG) from PA, are emerging as essential regulators fat metabolism, adipogenesis, organelle biogenesis. The mechanisms govern lipin translocation onto membranes largely unknown. Here we show recruitment the yeast (Pah1p) regulated by PA levels nuclear/endoplasmic reticulum (ER) membrane. Recruitment requires...
Changes in nuclear size and shape during the cell cycle or development require coordinated membrane remodeling, but underlying molecular events are largely unknown. We have shown previously that activity of conserved phosphatidate phosphatase Pah1p/Smp2p regulates structure yeast by controlling phospholipid synthesis biogenesis at envelope. Two screens for novel regulators led to identification DGK1. show Dgk1p is a unique diacylglycerol kinase uses CTP, instead ATP, generate phosphatidate....
The Saccharomyces cerevisiae PAH1-encoded Mg2+-dependent phosphatidate phosphatase (PAP1, 3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) catalyzes the dephosphorylation of to yield diacylglycerol and Pi. This enzyme plays a major role in synthesis triacylglycerols phospholipids S. cerevisiae. PAP1 contains DXDX(T/V) catalytic motif (DIDGT at residues 398-402) that is shared by mammalian fat-regulating protein lipin 1 superfamily haloacid dehalogenase-like proteins. yeast also conserved...
The human LPIN1 gene encodes the protein lipin 1, which possesses phosphatidate (PA) phosphatase (3-sn-phosphatidate phosphohydrolase; EC 3.1.3.4) activity (Han, G.-S., Wu, W.-I., and Carman, G. M. (2006) J. Biol. Chem. 281, 9210-9218). In this work, we characterized 1 alpha, beta, gamma isoforms that were expressed in Escherichia coli purified to near homogeneity. PA activities of dependent on Mg(2+) or Mn(2+) ions at pH 7.5 37 degrees C. inhibited by concentrations above their optimums...
Maintenance of energy homeostasis depends on the highly regulated storage and release triacylglycerol primarily in adipose tissue, excessive is a feature common metabolic disorders. CIDEA lipid droplet (LD)-protein enriched brown adipocytes promoting enlargement LDs, which are dynamic, ubiquitous organelles specialized for storing neutral lipids. We demonstrate an essential role this process amphipathic helix CIDEA, facilitates embedding LD phospholipid monolayer binds phosphatidic acid...
The Saccharomyces cerevisiae PAH1-encoded phosphatidate phosphatase (PAP) catalyzes the penultimate step in synthesis of triacylglycerol and plays a role transcriptional regulation phospholipid genes. PAP is phosphorylated at multiple Ser Thr residues dephosphorylated for vivo function by Nem1p-Spo7p protein complex localized nuclear/endoplasmic reticulum membrane. In this work, we characterized seven previously identified phosphorylation sites that are within Ser/Thr-Pro motif. When...
Lipids play crucial roles in many aspects of glial cell biology, affecting processes ranging from myelin membrane biosynthesis to axo-glial interactions. In order study the role lipid metabolism myelinating cells, we specifically deleted Schwann cells Lpin1 gene, which encodes Mg 2+ -dependent phosphatidate phosphatase (PAP1) enzyme necessary for normal triacylglycerol biosynthesis. The affected animals developed pronounced peripheral neuropathy characterized by degradation,...
Lipins are the founding members of a novel family Mg(2+)-dependent phosphatidate phosphatases (PAP1 enzymes) that play key roles in fat metabolism and lipid biosynthesis. Despite their importance, there is still little information on how activity regulated. Here we demonstrate functions lipin 1 2 evolutionarily conserved from unicellular eukaryotes to mammals. The two lipins display distinct intracellular localization HeLa M cells, with pool exhibiting tight membrane association. Small...
Lipins are evolutionarily conserved phosphatidate phosphatases that perform key functions in phospholipid, triglyceride, and membrane biogenesis. Translocation of lipins on membranes requires their dephosphorylation by the Nem1p-Spo7p transmembrane phosphatase complex through a poorly understood mechanism. Here we identify carboxy-terminal acidic tail yeast lipin Pah1p as an important regulator this step. Deletion or mutations disrupt binding to translocation. Overexpression drives...
Pah1p, which functions as phosphatidate phosphatase (PAP) in the yeast Saccharomyces cerevisiae, plays a crucial role lipid homeostasis by controlling relative proportions of its substrate and product diacylglycerol. The diacylglycerol produced PAP is used for synthesis triacylglycerol well phospholipids via Kennedy pathway. Pah1p highly phosphorylated protein vivo has been previously shown to be kinases Pho85p-Pho80p Cdc28p-cyclin B. In this work, we showed that was bona fide kinase A,...
The Saccharomyces cerevisiae DGK1 gene encodes a diacylglycerol kinase enzyme that catalyzes the formation of phosphatidate from diacylglycerol. Unlike kinases bacteria, plants, and animals, yeast utilizes CTP, instead ATP, as phosphate donor in reaction. Dgk1p contains CTP transferase domain is present SEC59-encoded dolichol CDS1-encoded CDP-diacylglycerol synthase enzymes. Deletion analysis showed was sufficient for activity. Point mutations (R76A, K77A, D177A, G184A) conserved residues...
Phosphatidate phosphatase (PAP) catalyzes the dephosphorylation of phosphatidate to yield diacylglycerol. In yeast Saccharomyces cerevisiae, PAP is encoded by PAH1, DPP1, and LPP1. The presence activity in pah1Δ dpp1Δ lpp1Δ triple mutant indicated another gene(s) encoding enzyme. We purified from salt extraction mitochondria followed chromatography with DE52, Affi-Gel Blue, phenyl-Sepharose, MonoQ, Superdex 200. Liquid chromatography/tandem mass spectrometry analysis a PAP-enriched sample...
Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and budding from ER. At molecular level, sole relevant interaction is that FITMs directly bind triacyglycerol diacylglycerol, but how they function at level not known. Saccharomyces cerevisiae has two FITM homologues: Scs3p Yft2p. was initially identified because deletion leads inositol auxotrophy, with an unusual sensitivity addition choline. This strongly...