Phospholipase D1

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PLD1
Identifiers
AliasesPLD1, phospholipase D1, CVDD
External IDsOMIM: 602382 MGI: 109585 HomoloGene: 116234 GeneCards: PLD1
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)[1]
Chromosome 3 (human)
Genomic location for PLD1
Genomic location for PLD1
Band3q26.31Start171,600,404 bp[1]
End171,810,950 bp[1]
RNA expression pattern
PBB GE PLD1 215724 at fs.png

PBB GE PLD1 177 at fs.png

PBB GE PLD1 215723 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001130081
NM_002662

NM_001164056
NM_008875
NM_001368667

RefSeq (protein)

NP_001123553
NP_002653

n/a

Location (UCSC)Chr 3: 171.6 – 171.81 MbChr 3: 27.94 – 28.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Phospholipase D1 (PLD1) is an enzyme that in humans is encoded by the PLD1 gene,[5][6] though analogues are found in plants, fungi, prokaryotes, and even viruses.[7]

History[edit]

The possibility of PLD1 was first mentioned in 1947 by authors Hanahan and Chaikoff at Berkeley when describing a carrot enzyme that could "[split] choline from phospholipids."[8] PLD was first derived in mammals in 1975 by Saito and Kanfer, who noted its activity in rats.[9] PLD was first cloned from HeLa cell cDNA in 1995, while mammalian PLD1 was first cloned from a rat in 1997.[7]

Function[edit]

Site of hydrolysis on a phosphatidylcholine by PLD1

Phosphatidylcholine (PC)-specific phospholipases D (PLDs) EC 3.1.4.4 catalyze the hydrolysis of PC to produce phosphatidic acid (PA) and choline. A range of agonists acting through G protein-coupled receptors and receptor tyrosine kinases stimulate this hydrolysis. PC-specific PLD activity has been implicated in numerous cellular pathways, including membrane trafficking, signal transduction, platelet coagulation, mitosis, apoptosis, and the creation of cytoplasmic lipid droplets (Hammond et al., 1995).[supplied by OMIM][7][10][11]

Membrane trafficking[edit]

Though biological activity of PLD1 is relatively low, it has been shown to associate at the plasma membrane, late endosome,[12] early endosome, and the Golgi apparatus.[7][9] It's thought that PA, a major product of PLD activity, is able to assist in negative membrane curvature due to its head group being smaller than in many other lipids.[7] One experiment with PLD1 knockout showed a significant reduction in the number of exocytotic fusion events, implying a strong role in exocytosis.[13]

Signal transduction[edit]

PLD1 may play a role in some cells in the endocytosis of signaling receptors or exocytosis of signaling molecules. For example, one experiment in B cells showed that limiting PLD1 led to significantly reduced endocytosis of the B cell receptor.[12] Another experiment showed that knocking out PLD1 may hinder the ability of mice to secrete catecholamines, molecules that are essential for vesicular communication across the body.[13]

Structure[edit]

Mammalian PLD1 has several domains for activators, inhibitors, and catalysis, which it shares with PLD2. Domains for both activation and inhibition are referred to as the phox homology (PX) and pleckstrin homology (PH) domains. The catalytic domain consists of two HKD regions, so named for three of the amino acids that are key in catalysis. These domains are conserved across many organisms.[7][9] There are two splice variants of the protein, PLD1a and PLD1b, but they do not seem to localize any differently.[7]

Applications[edit]

Alzheimer's Disease: PA, which is produced in part by PLD1, seems to be involved in the movement of β-amyloid, which could precede amyloidogenesis.[14]

Cancer: certain rat tumors with dominant negative PLD do not appear to form new colonies or tumors.[7][14]

Thrombosis: PLD knockout mice appear to have reduced occlusion, thus offsetting thrombosis.[7]

Type II Diabetes: the protein PED/PEA15 is often elevated in type II diabetic patients, thus enhancing PLD1 activity, and in turn impairing insulin.[7]

Interactions[edit]

Phospholipase D1 has been shown to interact with:

Inhibitors[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000075651 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027695 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Park SH, Chun YH, Ryu SH, Suh PG, Kim H (February 1999). "Assignment of human PLD1 to human chromosome band 3q26 by fluorescence in situ hybridization". Cytogenet Cell Genet. 82 (3–4): 224. doi:10.1159/000015105. PMID 9858822. S2CID 46791637.
  6. ^ Hammond SM, Altshuller YM, Sung TC, Rudge SA, Rose K, Engebrecht J, Morris AJ, Frohman MA (January 1996). "Human ADP-ribosylation factor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family". J Biol Chem. 270 (50): 29640–3. doi:10.1074/jbc.270.50.29640. PMID 8530346.
  7. ^ a b c d e f g h i j k Selvy, Paige E.; Lavieri, Robert R.; Lindsley, Craig W.; Brown, H. Alex (2011-10-12). "Phospholipase D: Enzymology, Functionality, and Chemical Modulation". Chemical Reviews. 111 (10): 6064–6119. doi:10.1021/cr200296t. ISSN 0009-2665. PMC 3233269. PMID 21936578.CS1 maint: PMC format (link)
  8. ^ Hanahan, Donald J.; Chaikoff, I. L. (1947-04-01). "THE PHOSPHORUS-CONTAINING LIPIDES OF THE CARROT". Journal of Biological Chemistry. 168 (1): 233–240. ISSN 0021-9258. PMID 20291081.
  9. ^ a b c Jenkins, G. M.; Frohman, M. A. (2005-10-01). "Phospholipase D: a lipid centric review". Cellular and Molecular Life Sciences CMLS. 62 (19): 2305–2316. doi:10.1007/s00018-005-5195-z. ISSN 1420-9071.
  10. ^ "Entrez Gene: PLD1 phospholipase D1, phosphatidylcholine-specific".
  11. ^ Andersson, L.; et al. (2006-05-09). "PLD1 and ERK2 regulate cytosolic lipid droplet formation". Journal of Cell Science. 119 (11): 2246–2257. doi:10.1242/jcs.02941. ISSN 0021-9533.
  12. ^ a b Donaldson, Julie G. (2009-09-01). "Phospholipase D in endocytosis and endosomal recycling pathways". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. Phospholipase D. 1791 (9): 845–849. doi:10.1016/j.bbalip.2009.05.011. ISSN 1388-1981.
  13. ^ a b Tanguy, Emeline; Costé de Bagneaux, Pierre; Kassas, Nawal; Ammar, Mohamed-Raafet; Wang, Qili; Haeberlé, Anne-Marie; Raherindratsara, Juliette; Fouillen, Laetitia; Renard, Pierre-Yves; Montero-Hadjadje, Maité; Chasserot-Golaz, Sylvette (2020-08). "Mono- and Poly-unsaturated Phosphatidic Acid Regulate Distinct Steps of Regulated Exocytosis in Neuroendocrine Cells". Cell Reports. 32 (7): 108026. doi:10.1016/j.celrep.2020.108026. ISSN 2211-1247. Check date values in: |date= (help)
  14. ^ a b Thakur, Rajan; Naik, Amruta; Panda, Aniruddha; Raghu, Padinjat (2019-06-04). "Regulation of Membrane Turnover by Phosphatidic Acid: Cellular Functions and Disease Implications". Frontiers in Cell and Developmental Biology. 7. doi:10.3389/fcell.2019.00083. ISSN 2296-634X.
  15. ^ Ahn BH, Rhim H, Kim SY, Sung YM, Lee MY, Choi JY, Wolozin B, Chang JS, Lee YH, Kwon TK, Chung KC, Yoon SH, Hahn SJ, Kim MS, Jo YH, Min DS (April 2002). "alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells". J. Biol. Chem. 277 (14): 12334–42. doi:10.1074/jbc.M110414200. PMID 11821392.
  16. ^ a b Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG (June 2000). "Inhibition of phospholipase D by amphiphysins". J. Biol. Chem. 275 (25): 18751–8. doi:10.1074/jbc.M001695200. PMID 10764771.
  17. ^ Walker SJ, Wu WJ, Cerione RA, Brown HA (May 2000). "Activation of phospholipase D1 by Cdc42 requires the Rho insert region". J. Biol. Chem. 275 (21): 15665–8. doi:10.1074/jbc.M000076200. PMID 10747870.
  18. ^ Zhang Y, Redina O, Altshuller YM, Yamazaki M, Ramos J, Chneiweiss H, Kanaho Y, Frohman MA (November 2000). "Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein that interacts with them". J. Biol. Chem. 275 (45): 35224–32. doi:10.1074/jbc.M003329200. PMID 10926929.
  19. ^ Oishi K, Takahashi M, Mukai H, Banno Y, Nakashima S, Kanaho Y, Nozawa Y, Ono Y (May 2001). "PKN regulates phospholipase D1 through direct interaction". J. Biol. Chem. 276 (21): 18096–101. doi:10.1074/jbc.M010646200. PMID 11259428.
  20. ^ Luo JQ, Liu X, Hammond SM, Colley WC, Feig LA, Frohman MA, Morris AJ, Foster DA (June 1997). "RalA interacts directly with the Arf-responsive, PIP2-dependent phospholipase D1". Biochem. Biophys. Res. Commun. 235 (3): 854–9. doi:10.1006/bbrc.1997.6793. PMID 9207251.
  21. ^ Kim JH, Lee SD, Han JM, Lee TG, Kim Y, Park JB, Lambeth JD, Suh PG, Ryu SH (July 1998). "Activation of phospholipase D1 by direct interaction with ADP-ribosylation factor 1 and RalA". FEBS Lett. 430 (3): 231–5. doi:10.1016/s0014-5793(98)00661-9. PMID 9688545. S2CID 36075513.
  22. ^ Genth H, Schmidt M, Gerhard R, Aktories K, Just I (February 2003). "Activation of phospholipase D1 by ADP-ribosylated RhoA". Biochem. Biophys. Res. Commun. 302 (1): 127–32. doi:10.1016/s0006-291x(03)00112-8. PMID 12593858.
  23. ^ Cai S, Exton JH (May 2001). "Determination of interaction sites of phospholipase D1 for RhoA". Biochem. J. 355 (Pt 3): 779–85. doi:10.1042/bj3550779. PMC 1221795. PMID 11311142.
  24. ^ Lewis JA, Scott SA, Lavieri R, Buck JR, Selvy PE, Stoops SL, Armstrong MD, Brown HA, Lindsley CW (April 2009). "Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: Impact of alternative halogenated privileged structures for PLD1 specificity". Bioorg. Med. Chem. Lett. 19 (7): 1916–20. doi:10.1016/j.bmcl.2009.02.057. PMC 3791604. PMID 19268584.

Further reading[edit]