title: Internal and surface-localized major surface proteases of Leishmania spp. and their differential release from promastigotes.
abstract: Major surface protease (MSP), also called GP63, is a virulence factor of Leishmania spp. protozoa. There are three pools of MSP, located either internally within the parasite, anchored to the surface membrane, or released into the extracellular environment. The regulation and biological functions of these MSP pools are unknown. We investigated here the trafficking and extrusion of surface versus internal MSPs. Virulent Leishmania chagasi undergo a growth-associated lengthening in the t(1/2) of surface-localized MSP, but this did not occur in the attenuated L5 strain. The release of surface-localized MSP was enhanced in a dose-dependent manner by MbetaCD, which chelates membrane cholesterol-ergosterol. Furthermore, incubation of promastigotes at 37 degrees C with Matrigel matrix, a soluble basement membrane extract of Engelbreth-Holm-Swarm tumor cells, stimulated the release of internal MSP but not of surface-located MSP. Taken together, these data indicate that MSP subpopulations in distinct cellular locations are released from the parasite under different environmental conditions. We hypothesize that the internal MSP with its lengthy t(1/2) does not serve as a pool for promastigote surface MSP in the sand fly vector but that it instead functions as an MSP pool ready for quick release upon inoculation of metacyclic promastigotes into mammals. We present a model in which these different MSP pools are released under distinct life cycle-specific conditions.
authors: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. chaoqun-yao@uiowa.edu
authors: Chaoqun
authors: C
authors: Yao
authors: John E
authors: JE
authors: Donelson
authors: Mary E
authors: ME
authors: Wilson
mesh_terms: D000818:Animals; D002999:Clone Cells; D003094:Collagen; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D007527:Isoenzymes / Q000378:metabolism; D007797:Laminin; D007891:Leishmania / Q000166:cytology* / Q000201:enzymology* / Q000472:pathogenicity; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000378:metabolism*; D011509:Proteoglycans; D013696:Temperature; D014774:Virulence / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D004338:Drug Combinations; D007527:Isoenzymes; D007797:Laminin; D011509:Proteoglycans; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C059485:matrigel; D003094:Collagen; D010447:Peptide Hydrolases
references: Proc Natl Acad Sci U S A. 2001 May 8;98(10):5815-20
references: 11309494
references: Parasitology. 2006 Jan;132(Pt 1):37-47
references: 16393352
references: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13072-7
references: 11698680
references: J Biol Chem. 2002 Mar 15;277(11):8802-9
references: 11777912
references: Mol Biochem Parasitol. 2002 Apr 30;121(1):119-28
references: 11985868
references: Infect Immun. 2003 Feb;71(2):1008-10
references: 12540585
references: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5813-8
references: 12724530
references: Blood. 2003 Jul 1;102(1):215-22
references: 12637320
references: Parasitol Res. 2003 Oct;91(3):229-37
references: 12923634
references: Mol Biochem Parasitol. 2003 Nov;132(1):1-16
references: 14563532
references: Mol Biochem Parasitol. 2004 Feb;133(2):145-52
references: 14698427
references: J Immunol. 2004 Apr 1;172(7):4324-31
references: 15034047
references: Mol Biochem Parasitol. 2004 Jun;135(2):171-83
references: 15110459
references: Microbes Infect. 2004 Jun;6(7):646-9
references: 15158771
references: Comp Immunol Microbiol Infect Dis. 2004 Sep;27(5):305-18
references: 15225981
references: Microbes Infect. 2004 Jul;6(9):864-73
references: 15374009
references: J Biol Chem. 1981 Feb 25;256(4):1604-7
references: 6257680
references: Proc Natl Acad Sci U S A. 1986 Aug;83(16):5988-91
references: 3461472
references: Exp Parasitol. 1989 Jul;69(1):100-3
references: 2659372
references: J Immunol. 1989 Jul 15;143(2):678-84
references: 2738406
references: Mol Cell Biol. 1990 Mar;10(3):1084-94
references: 2304458
references: J Clin Invest. 1991 Nov;88(5):1511-21
references: 1658042
references: J Biol Chem. 1992 Jan 25;267(3):1888-95
references: 1370484
references: Acta Trop. 1992 Feb;50(3):205-17
references: 1348597
references: World Health Stat Q. 1992;45(2-3):267-75
references: 1462660
references: Mol Biochem Parasitol. 1993 Mar;58(1):107-21
references: 8459823
references: Mol Biochem Parasitol. 1993 Dec;62(2):157-71
references: 8139613
references: Mol Biochem Parasitol. 1994 Aug;66(2):201-10
references: 7808470
references: Biochim Biophys Acta. 1995 Dec 6;1253(2):199-207
references: 8519803
references: J Biol Chem. 1997 Oct 17;272(42):26742-8
references: 9334260
references: Mol Biochem Parasitol. 1998 May 15;93(1):31-41
references: 9662026
references: Nature. 1999 Apr 15;398(6728):618-22
references: 10217144
references: Parasitology. 2006 Feb;132(Pt 2):177-85
references: 16197592
references: An Acad Bras Cienc. 2006 Dec;78(4):687-714
references: 17143406
references: Exp Parasitol. 2007 Aug;116(4):354-60
references: 17368448
references: Nat Genet. 2007 Jul;39(7):839-47
references: 17572675
references: Parasitol Today. 2000 Jan;16(1):28-30
references: 10637585
references: J Biol Chem. 2000 Oct 27;275(43):33883-9
references: 10931831
references: J Cell Sci. 2000 Dec;113 Pt 24:4587-603
references: 11082051
references: Mol Biochem Parasitol. 2001 Jan 15;112(1):51-9
references: 11166386
references: J Biol Chem. 1993 Jul 25;268(21):15731-6
references: 8340397
references: Cardiovasc Res. 2004 Dec 1;64(3):507-15
references: 15537504
references: Cancer Res. 2004 Dec 15;64(24):8831-8
references: 15604241
references: Mol Biochem Parasitol. 2005 Feb;139(2):173-83
references: 15664652
references: Mol Biochem Parasitol. 2005 Jul;142(1):88-97
references: 15876463
references: Science. 2005 Jul 15;309(5733):409-15
references: 16020725
references: Parasitology. 2005 Aug;131(Pt 2):207-14
references: 16145937
references: Mol Biochem Parasitol. 2001 Sep 28;117(1):1-10
references: 11551627