A Novel Family of IMC Proteins Displays a Hierarchical Organization and Functions in Coordinating Parasite Division

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Apicomplexans employ a peripheral membrane system called the inner membrane complex (IMC) for critical processes such as host cell invasion and daughter cell formation. We have identified a family of proteins that define novel sub-compartments of the Toxoplasma gondii IMC. These IMC Sub-compartment Proteins, ISP1, 2 and 3, are conserved throughout the Apicomplexa, but do not appear to be present outside the phylum. ISP1 localizes to the apical cap portion of the IMC, while ISP2 localizes to a central IMC region and ISP3 localizes to a central plus basal region of the complex. Targeting of all three ISPs is dependent upon N-terminal residues predicted for coordinated myristoylation and palmitoylation. Surprisingly, we show that disruption of ISP1 results in a dramatic relocalization of ISP2 and ISP3 to the apical cap. Although the N-terminal region of ISP1 is necessary and sufficient for apical cap targeting, exclusion of other family members requires the remaining C-terminal region of the protein. This gate-keeping function of ISP1 reveals an unprecedented mechanism of interactive and hierarchical targeting of proteins to establish these unique sub-compartments in the Toxoplasma IMC. Finally, we show that loss of ISP2 results in severe defects in daughter cell formation during endodyogeny, indicating a role for the ISP proteins in coordinating this unique process of Toxoplasma replication.

Vyšlo v časopise: A Novel Family of IMC Proteins Displays a Hierarchical Organization and Functions in Coordinating Parasite Division. PLoS Pathog 6(9): e32767. doi:10.1371/journal.ppat.1001094
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001094

Souhrn

Zdroje

1. HillDE

ChirukandothS

DubeyJP

2005 Biology and epidemiology of Toxoplasma gondii in man and animals. Anim Health Res Rev 6 41 61

2. SondaS

HehlAB

2006 Lipid biology of Apicomplexa: perspectives for new drug targets, particularly for Toxoplasma gondii. Trends Parasitol 22 41 47

3. GherardiA

SarcironME

2007 Molecules targeting the purine salvage pathway in Apicomplexan parasites. Trends Parasitol 23 384 389

4. McFaddenGI

RoosDS

1999 Apicomplexan plastids as drug targets. Trends Microbiol 7 328 333

5. KeelingPJ

BurgerG

DurnfordDG

LangBF

LeeRW

2005 The tree of eukaryotes. Trends Ecol Evol 20 670 676

6. GouldSB

ThamWH

CowmanAF

McFaddenGI

WallerRF

2008 Alveolins, a new family of cortical proteins that define the protist infrakingdom Alveolata. Mol Biol Evol 25 1219 1230

7. TrempAZ

KhaterEI

DessensJT

2008 IMC1b is a putative membrane skeleton protein involved in cell shape, mechanical strength, motility, and infectivity of malaria ookinetes. J Biol Chem 283 27604 27611

8. LauRK

KwokAC

ChanWK

ZhangTY

WongJT

2007 Mechanical characterization of cellulosic thecal plates in dinoflagellates by nanoindentation. J Nanosci Nanotechnol 7 452 457

9. StellyN

MaugerJP

ClaretM

AdoutteA

1991 Cortical alveoli of Paramecium: a vast submembranous calcium storage compartment. J Cell Biol 113 103 112

10. StellyN

HalpernS

NicolasG

FraguP

AdoutteA

1995 Direct visualization of a vast cortical calcium compartment in Paramecium by secondary ion mass spectrometry (SIMS) microscopy: possible involvement in exocytosis. J Cell Sci 108 (Pt 5) 1895 1909

11. PlattnerH

KlaukeN

2001 Calcium in ciliated protozoa: sources, regulation, and calcium-regulated cell functions. Int Rev Cytol 201 115 208

12. D'HaeseJ

MehlhornH

PetersW

1977 Comparative electron microscope study of pellicular structures in coccidia (Sarcocystis, Besnoitia and Eimeria). Int J Parasitol 7 505 518

13. MannT

BeckersC

2001 Characterization of the subpellicular network, a filamentous membrane skeletal component in the parasite Toxoplasma gondii. Mol Biochem Parasitol 115 257 268

14. PorchetE

TorpierG

1977 [Freeze fracture study of Toxoplasma and Sarcocystis infective stages (author's transl)]. Z Parasitenkd 54 101 124

15. CintraWM

de SouzaW

1985 Distribution of intramembranous particles and filipin-sterol complexes in the cell membranes of Toxoplasma gondii. Eur J Cell Biol 37 63 69

16. DubremetzJF

TorpierG

1978 Freeze fracture study of the pellicle of an eimerian sporozoite (Protozoa, Coccidia). J Ultrastruct Res 62 94 109

17. MorrissetteNS

MurrayJM

RoosDS

1997 Subpellicular microtubules associate with an intramembranous particle lattice in the protozoan parasite Toxoplasma gondii. J Cell Sci 110 (Pt 1) 35 42

18. KeeleyA

SoldatiD

2004 The glideosome: a molecular machine powering motility and host-cell invasion by Apicomplexa. Trends Cell Biol 14 528 532

19. StriepenB

JordanCN

ReiffS

van DoorenGG

2007 Building the perfect parasite: cell division in apicomplexa. PLoS Pathog 3 e78

20. HuK

JohnsonJ

FlorensL

FraunholzM

SuravajjalaS

2006 Cytoskeletal components of an invasion machine—the apical complex of Toxoplasma gondii. PLoS Pathog 2 e13

21. GubbelsMJ

WhiteM

SzatanekT

2008 The cell cycle and Toxoplasma gondii cell division: tightly knit or loosely stitched? Int J Parasitol 38 1343 1358

22. GilkSD

RavivY

HuK

MurrayJM

BeckersCJ

2006 Identification of PhIL1, a novel cytoskeletal protein of the Toxoplasma gondii pellicle, through photosensitized labeling with 5-[125I]iodonaphthalene-1-azide. Eukaryot Cell 5 1622 1634

23. GaskinsE

GilkS

DeVoreN

MannT

WardG

2004 Identification of the membrane receptor of a class XIV myosin in Toxoplasma gondii. J Cell Biol 165 383 393

24. BullenHE

TonkinCJ

O'DonnellRA

ThamWH

PapenfussAT

2009 A novel family of Apicomplexan glideosome-associated proteins with an inner membrane-anchoring role. J Biol Chem 284 25353 25363

25. RayavaraK

RajapandiT

WollenbergK

KabatJ

FischerER

2009 A complex of three related membrane proteins is conserved on malarial merozoites. Mol Biochem Parasitol 167 135 143

26. de MiguelN

LebrunM

HeaslipA

HuK

BeckersCJ

2008 Toxoplasma gondii Hsp20 is a stripe-arranged chaperone-like protein associated with the outer leaflet of the inner membrane complex. Biol Cell 100 479 489

27. ChaudharyK

DonaldRG

NishiM

CarterD

UllmanB

2005 Differential localization of alternatively spliced hypoxanthine-xanthine-guanine phosphoribosyltransferase isoforms in Toxoplasma gondii. J Biol Chem 280 22053 22059

28. DeRocherAE

CoppensI

KarnatakiA

GilbertLA

RomeME

2008 A thioredoxin family protein of the apicoplast periphery identifies abundant candidate transport vesicles in Toxoplasma gondii. Eukaryot Cell 7 1518 1529

29. Maurer-StrohS

EisenhaberB

EisenhaberF

2002 N-terminal N-myristoylation of proteins: prediction of substrate proteins from amino acid sequence. J Mol Biol 317 541 557

30. RenJ

WenL

GaoX

JinC

XueY

2008 CSS-Palm 2.0: an updated software for palmitoylation sites prediction. Protein Eng Des Sel 21 639 644

31. TilleyM

UptonSJ

FayerR

BartaJR

ChrispCE

1991 Identification of a 15-kilodalton surface glycoprotein on sporozoites of Cryptosporidium parvum. Infect Immun 59 1002 1007

32. JenkinsMC

FayerR

TilleyM

UptonSJ

1993 Cloning and expression of a cDNA encoding epitopes shared by 15- and 60-kilodalton proteins of Cryptosporidium parvum sporozoites. Infect Immun 61 2377 2382

33. WichroskiMJ

MeltonJA

DonahueCG

TwetenRK

WardGE

2002 Clostridium septicum alpha-toxin is active against the parasitic protozoan Toxoplasma gondii and targets members of the SAG family of glycosylphosphatidylinositol-anchored surface proteins. Infect Immun 70 4353 4361

34. StokkermansTJ

SchwartzmanJD

KeenanK

MorrissetteNS

TilneyLG

1996 Inhibition of Toxoplasma gondii replication by dinitroaniline herbicides. Exp Parasitol 84 355 370

35. MorrissetteNS

SibleyLD

2002 Disruption of microtubules uncouples budding and nuclear division in Toxoplasma gondii. J Cell Sci 115 1017 1025

36. ShawMK

ComptonHL

RoosDS

TilneyLG

2000 Microtubules, but not actin filaments, drive daughter cell budding and cell division in Toxoplasma gondii. J Cell Sci 113 (Pt 7) 1241 1254

37. ReshMD

2006 Trafficking and signaling by fatty-acylated and prenylated proteins. Nat Chem Biol 2 584 590

38. HuynhMH

CarruthersVB

2009 Tagging of endogenous genes in a Toxoplasma gondii strain lacking Ku80. Eukaryot Cell 8 530 539

39. SalisburyJL

1995 Centrin, centrosomes, and mitotic spindle poles. Curr Opin Cell Biol 7 39 45

40. NicholsBA

ChiappinoML

1987 Cytoskeleton of Toxoplasma gondii. J Protozool 34 217 226

41. SheffieldHG

MeltonML

1968 The fine structure and reproduction of Toxoplasma gondii. J Parasitol 54 209 226

42. HuK

2008 Organizational changes of the daughter basal complex during the parasite replication of Toxoplasma gondii. PLoS Pathog 4 e10

43. GubbelsMJ

VaishnavaS

BootN

DubremetzJF

StriepenB

2006 A MORN-repeat protein is a dynamic component of the Toxoplasma gondii cell division apparatus. J Cell Sci 119 2236 2245

44. HeaslipAT

DzierszinskiF

SteinB

HuK

e1000754 TgMORN1 is a key organizer for the basal complex of Toxoplasma gondii. PLoS Pathog 6

45. NadolskiMJ

LinderME

2009 Molecular recognition of the palmitoylation substrate Vac8 by its palmitoyltransferase Pfa3. J Biol Chem 284 17720 17730

46. SwarthoutJT

LoboS

FarhL

CrokeMR

GreentreeWK

2005 DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras. J Biol Chem 280 31141 31148

47. ZhaoL

LoboS

DongX

AultAD

DeschenesRJ

2002 Erf4p and Erf2p form an endoplasmic reticulum-associated complex involved in the plasma membrane localization of yeast Ras proteins. J Biol Chem 277 49352 49359

48. SmotrysJE

LinderME

2004 Palmitoylation of intracellular signaling proteins: regulation and function. Annu Rev Biochem 73 559 587

49. SaricM

VahrmannA

NieburD

KluempersV

HehlAB

2009 Dual acylation accounts for the localization of {alpha}19-giardin in the ventral flagellum pair of Giardia lamblia. Eukaryot Cell 8 1567 1574

50. EmmerBT

SoutherC

TorielloKM

OlsonCL

EptingCL

2009 Identification of a palmitoyl acyltransferase required for protein sorting to the flagellar membrane. J Cell Sci 122 867 874

51. HuK

MannT

StriepenB

BeckersCJ

RoosDS

2002 Daughter cell assembly in the protozoan parasite Toxoplasma gondii. Mol Biol Cell 13 593 606

52. HuK

RoosDS

AngelSO

MurrayJM

2004 Variability and heritability of cell division pathways in Toxoplasma gondii. J Cell Sci 117 5697 5705

53. FergusonDJ

SahooN

PinchesRA

BumsteadJM

TomleyFM

2008 MORN1 has a conserved role in asexual and sexual development across the apicomplexa. Eukaryot Cell 7 698 711

54. DonaldRG

CarterD

UllmanB

RoosDS

1996 Insertional tagging, cloning, and expression of the Toxoplasma gondii hypoxanthine-xanthine-guanine phosphoribosyltransferase gene. Use as a selectable marker for stable transformation. J Biol Chem 271 14010 14019

55. BradleyPJ

WardC

ChengSJ

AlexanderDL

CollerS

2005 Proteomic analysis of rhoptry organelles reveals many novel constituents for host-parasite interactions in Toxoplasma gondii. J Biol Chem 280 34245 34258

56. BurgJL

PerelmanD

KasperLH

WarePL

BoothroydJC

1988 Molecular analysis of the gene encoding the major surface antigen of Toxoplasma gondii. J Immunol 141 3584 3591

57. SchwartzmanJD

KrugEC

1989 Toxoplasma gondii: characterization of monoclonal antibodies that recognize rhoptries. Exp Parasitol 68 74 82

58. HarlowE

LaneD

1988 Immunoaffinity purification.Antibodies: a laboratory manual. Cold Spring Harbor NY Cold Spring Harbor Laboratory 511 533