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I mznzreuiewb. I Lipids of Paramecium Edna S. Kaneshim Department of Biological Sciences, University of Cincinnati, Cincinnati, OH 45221-0006 Abstract This review is the first on the composition and metab- I. Paramecium, a eukaryotic protozoan used for the olism of Pammcciwn lipids. This ciliated protozoa is a useful study of membranes system for studying the structure and function of biomembranes since it can be grown under chemically defined culture condi- In the period from 1930 into the 1970s substantial pro- tions in large numbers; much is known about its genetics, mem- gress was made on the understanding of nuclear divisions, brane electrophysiology, and ultrastructure; and mutants with mating, and genetics of P. aurelia, primarily by Sonneborn defective membrane functions are available which are reported Preer and their colleagues. During the same to have lipid alterations. Pure preparations of the cell surface (1, 2) (3), ciliary membrane are readily isolated. The organism and its period, significant advances were made on the understand- ciliary membrane contain a variety of polar lipids, sterols, and ing of membrane electrophysiological events of I! cauda- Downloaded from steryl esters. The polar lipids include substantial amounts of tum by workers such as Kamada and Kinosita (4-6), and ether lipids, sphingolipids, and phosphonolipids. The biosyn- later by Naitoh, Eckert, and others (7-9). Being a larger theses of fatty acids and specific moieties of complex lipids in this cell than aurelia, I! caudatum was easier to manipulate organism are beginning to be examined with promises of elu- I? cidating biosynthetic mechanisms that are more difficult to for intracellular recordings of membrane electrical re- study in other organisms. More information on lipid metabo- sponses. Current technology enables similar studies on E! www.jlr.org lism is required to identify the bases for the defects in putative aurelia (see below). The avoidance reaction (10) in Parame- lipid/membrane mutants. - Kaneshim, E. S. Lipids of Pammc- cium was explained by the Ca2+ hypothesis (7-9). cium. J. Lipid Res. 1987. 28: 1241 - 1258. Depolarization of the surface membrane activates by guest, on February 4, 2012 Supplementary key words cilia ether lipids membranes phos- voltage-sensitive Ca2+channels in the ciliary membrane phonolipids sphingolipids ciliated protom ion channels mutants (11, 12). The opening of these channels permits extracel- thermal avoidance lular Ca2+to move down its concentration gradient into the cilia. The increased intraciliary Ca2*levels trigger the TABLE OF CONTENTS reversal of the effective stroke of ciliary beat resulting in I. Paramecium, a Eukaryotic Protozoan Used AbbIwiations: AEP, &oethyIphcepbMte; AP*, 2-&0-3-pha~ph0- for the Study of Membranes 1241 nopmpanate; m, adenosine triphosphate; CoA,coenyme A; CL, doli- 11. Lipid Nutritional Requirements for pin, CMP, cytidine monophcephate; DPnE, N-acyl-sphingank-1-phospho- noethanolamine, N-acyl-dihydmsphingine-1-phosphonoethanolamine; Growth of Paramecium 1242 DPsE, N-acyl-sphinganine-1-phosphoethanolamine,N-acyl-dihydro- 111. Uptake of Lipids 1242 sphingosine-1-phosphoethanolamine;GTP, guanosine triphosphate; IPS, IV. Total Lipids 1243 inositol triphosphate; LCB, long-chain base; PA, phosphatidic acid; PC, 1,2-diacyl-sn-glycero-3-phosphocholineand 1-alkyl, P-acyl-sn-glycero- V. Fatty Acids 1245 3-phosphocholine; PEP, phosphoenolpyruvate; PI, 1,2-diacyl-sn-glycero- VI. Neutral Lipids 1249 3-phosphoinositol and l-alkyl-2-acyl-sn-glycero-3-phosphoinosit01,phos- A. Sterols 1249 phatidylinositol; PI-P, phosphatidylinositol phosphate; PI-P2, phos- phatidylinositol diphosphate; PnE, 1,2-diacyl-m-glycero-3-(2-amino- B. Fatty acids 1249 ethy1)phosphonate and 1-alkyl, 2-acyl-sn-glycer0-3-(2-aminmthyl)phos- C. Neutral sphingolipids 1250 phonate; PPnE, N-acyl-h..-4-hyd~phmganine-l-phcephonoethanol- VII. Polar Lipids 1250 amine, N-acyl-phytosphingosine-1-phosphonoethanolamine;PPsE, N- acyl-tmnr-4-hydroxysphinganine-l-phosphoethanolamine, N-acyl-phy- A. Phosphonolipids 1250 tosphingosine-1-phosphoethanolamine;PS, 1,2-diacyl-sn-glycero-3-phos- B. Ether lipids 1250 phoserine and 1-alkyl, 2-acyl-sn-glycero-3-phosphoserine;PsE, 1,Z-di- C. Sphingolipids acyl-sn-glycero-3-(2-aminoethyl)phosphateand 1-alkyl, 2-acyl-sn-3-(2- 1252 amino-ethyl) phosphate; PUFA, polyunsaturated fatty acids; RSA, D. Inositol lipid metabolism 1253 relative specific activity; SFA, saturated fatty acids; SPL, sphingophos- VIII. Mutants 1253 pholipids and sphingophosphonolipids; SPnE, N-acyl-sphingenine- IX. Culture Age and Temperature Effects 1254 l-phosphonoethanolaminq N-acyl-sphinpinephcephoncdandamine;SPsE, N-acyl-sphinpcni.cl-pbosphoethanolamine, N-acyl-sphingosine-l-phospho- X. Conclusions 1256 ethanolamine; UI, unsaturation index. Journal of Lipid Research Volume 28, 1987 1241 backward swimming. The channel is inactivated or closed currently known about the lipids of other species, thus, by elevated intraciliary Ca2+levels (13); and membrane unless otherwise indicated, this review will be on the ATPases (14, 15) pump Ca2+out during the renormaliza- lipids of this species. tion period during which the cell pivots around its posterior end (10). When intraciliary Ca2+levels are suffi- 11. Lipid nutritional requirements for growth of ciently decreased, the cell swims in the normal forward Paramecium direction. After Kung (16) isolated a membrane (be- The first ciliated protozoan that was found to require havioral) mutant of l? tetraurelia and, with Eckert and lipids for growth was Paramecium. This organism requires Naitoh (17, 18), demonstrated that the pawn mutant had a Cz4 alkyl-substituted sterol with a double bond at the A5 defective membrane voltage-sensitive Ca2+channels, the or the A7 position, best fulfilled by stigmasterol or pori- species of choice for most biochemical studies has been P ferasterol (33, 34). It also needs a fatty acid and/or com- tetraurelia. Over 300 membrane mutant lines representing plex lipids containing fatty acids. Paramecium aurelia has a more than 25 complementation groups have since been stringent requirement for oleic acid, presumably being isolated (19, 20). In many cases, the mutations have been unable to desaturate stearate (34). The fatty acids re- correlated with altered membrane electrical properties. quired by other species such as ? multimictonucleatum, f! Paramecium aurelia is not only a useful unicellular calkinsi, and ? caudatum may be different. The reader is eukaryotic system for studying the structure and function referred to a review of earlier nutritional studies by Van of electrically excitable membranes, but this ciliate also Wagtendonk (34) who was the investigator primarily serves as a model for exocytosis. The extrusion organelle, responsible for the establishment of axenic cultures and the trichocyst, is synthesized and assembled in the cyto- the eventual formulation of chemically defined media for Downloaded from plasm, moves to the cell surface, docks at predetermined the growth of Paramecium which made reliable biochemical sites at the cell surface where it attaches to the cell mem- studies possible utilizing this ciliated unicell. To date, a brane, and the contents of the membrane-bound or- comprehensive review of the lipids of Paramecium has not ganelle are released upon fusion of trichocyst and cell been published. surface membranes (21-25). Membrane fusion results Although studies of l? tetraurelia lipids have been done from events triggered by an appropriate stimulus and in- on cells grown in a grass (Cerophyl) or lettuce extract with www.jlr.org volves an influx of Ca2+(22, 23). Defects at different steps bacteria, most of the lipids identified and characterized in trichocyst release in mutants have been correlated with have been documented by analyses of lipids from axen- altered intramembranous particle arrays suggesting ically grown cells. This review focuses on the latter by guest, on February 4, 2012 specific functions for different arrays. The “ring” and studies. A modified (35) enriched crude medium (34) that “rosette” arrays are in the cell surface membrane and the includes stigmasterol, phosphatidylethanolamine (PsE), “annulus” is in the trichocyst membrane (21, 23-25). Non- and a mixture of fatty acids is commonly used. Peptones discharge mutants have been isolated that are either and crude RNA preparations in this medium are not defective in the formation of trichocysts, fail to attach usually lipid-free and often contain fatty acids and sterols. trichocysts to preformed sites at the cell membrane (ab- Also, some commercially available phospholipids contain normal “annulus” or “ring”), or fail to respond to stimuli sterol contaminants. In some studies a chemically defined even when properly docked (defective “rosette”) (21, medium containing the same lipid supplements as those 23-25). included in the crude medium is used (29, 34, 35). In Paramecium tetraurelia has more recently been developed other studies that require stringent, defined conditions, as a system for understanding chemoreception and the stigmasterol and either oleate, monolein, or synthetic di- nature of receptor binding and signal transduction in che- oleoyl PsE are the only lipids included in the chemically motaxis (26, 27). Attractants such as folic acid have been defined medium (29, 34, 35). shown to bind to surface membrane receptor sites. Bind- ing of an attractant is correlated with hyperpolarization of 111. Uptake of lipids the cell membrane and increased
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  • The TMEM189 Gene Encodes Plasmanylethanolamine Desaturase Which Introduces the Characteristic Vinyl Ether Double Bond Into Plasmalogens

    The TMEM189 Gene Encodes Plasmanylethanolamine Desaturase Which Introduces the Characteristic Vinyl Ether Double Bond Into Plasmalogens

    The TMEM189 gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens Ernst R. Wernera,1, Markus A. Kellerb, Sabrina Sailera, Katharina Lacknera, Jakob Kochb, Martin Hermannc, Stefan Coassind, Georg Golderera, Gabriele Werner-Felmayera, Raphael A. Zoellere, Nicolas Hulof, Johannes Bergerg, and Katrin Watschingera,1 aInstitute of Biological Chemistry, Biocenter, Medical University of Innsbruck, A-6020 Innsbruck, Austria; bInstitute of Human Genetics, Medical University of Innsbruck, A-6020 Innsbruck, Austria; cUniversity Clinic for Anesthesiology and General Intensive Care Medicine, Medical University of Innsbruck, A-6020 Innsbruck, Austria; dInstitute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, A-6020 Innsbruck, Austria; eDepartment of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118; fInstitute of Genetics and Genomics, University of Geneva, 1211 Geneva 4, Switzerland; and gDepartment of Pathobiology of the Nervous System, Medical University of Vienna, 1090 Vienna, Austria Edited by Benjamin F. Cravatt, Scripps Research Institute, La Jolla, CA, and approved February 26, 2020 (received for review October 7, 2019) A significant fraction of the glycerophospholipids in the human body severe clinical outcomes, including impaired neural development, is composed of plasmalogens, particularly in the brain, cardiac, and bone deformation, and premature death. The initial peroxisomal immune cell membranes. A decline in these lipids has been observed steps of human plasmalogen biosynthesis have been well charac- in such diseases as Alzheimer’s and chronic obstructive pulmonary terized to require the genes GNPAT (11, 12), AGPS (13), and disease. Plasmalogens contain a characteristic 1-O-alk-1′-enyl ether DHRS7B (14). Further downstream steps occurring in the en- (vinyl ether) double bond that confers special biophysical, biochemi- doplasmic reticulum are less well understood, however.