Academic Journal
The Plasmodium GRASP Homolog Modulates Liver Stage Development, Subsequent Blood Infection and Virulence in Mice.
| Τίτλος: | The Plasmodium GRASP Homolog Modulates Liver Stage Development, Subsequent Blood Infection and Virulence in Mice. |
|---|---|
| Συγγραφείς: | Gehrke EJ; Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA., Sahu T; Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA., Manuguri KS; Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA., Voss C; Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA., Mlambo G; Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA., Asady B; Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA., Saffarian M; Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA., Romano JD; Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA., Coppens I; Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA. |
| Πηγή: | Molecular microbiology [Mol Microbiol] 2025 Jun; Vol. 123 (6), pp. 487-515. Date of Electronic Publication: 2025 Mar 26. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 8712028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2958 (Electronic) Linking ISSN: 0950382X NLM ISO Abbreviation: Mol Microbiol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford, OX ; Boston, MA : Blackwell Scientific Publications, c1987- |
| Ιατρικοί όροι (MeSH): | Plasmodium berghei*/pathogenicity , Plasmodium berghei*/growth & development , Plasmodium berghei*/genetics , Plasmodium berghei*/metabolism , Liver*/parasitology , Malaria*/parasitology , Protozoan Proteins*/metabolism , Protozoan Proteins*/genetics , Golgi Matrix Proteins*/metabolism , Golgi Matrix Proteins*/genetics, Hepatocytes/parasitology ; Golgi Apparatus/metabolism ; Autophagosomes/metabolism ; Merozoites/metabolism ; Merozoites/growth & development ; Parasitemia/parasitology ; Animals ; Mice ; Virulence ; Autophagy ; Female |
| Περίληψη: | Conserved across eukaryotic cells, Golgi reassembly and stacking proteins (GRASPs) are peripheral proteins that hold the flat cisternal membranes of the Golgi apparatus into stacks and that also play a role in a process of unconventional protein secretion involving the autophagy machinery. The Golgi in Plasmodium malaria parasites is composed of unstacked cisternae that contain a single GRASP homolog. We previously showed that the initial development of Plasmodium berghei in hepatocytes involves the clearance of micronemes through their sequestration into PbATG8-positive autophagosomes that fuse with the parasite plasma membrane. Here, we examine the involvement of PbGRASP in microneme elimination and extend our studies to assess the importance of GRASP for parasite development in the mammalian host and mosquito vector. GRASP associates with PbATG8 autophagosomes containing micronemes, though PbGRASP-KO parasites can expel micronemes. PbGRASP-KO parasites have no discernable phenotype during mosquito stage development or asexual blood stage growth. PbGRASP-KO liver stages form small schizonts at mid-infection, and then growth resumes. PbGRASP-KO hepatic merozoites egress from the mouse liver and induce higher parasitemia but display delayed and reduced cerebral malaria symptoms. These observations point to a regulatory role for GRASP in controlling parasite proliferation and virulence in mammalian hosts. (© 2025 John Wiley & Sons Ltd.) |
| References: | Nat Commun. 2016 May 26;7:11659. (PMID: 27225796) Methods Mol Biol. 2016;1459:31-46. (PMID: 27665549) J Cell Biol. 2007 Jan 29;176(3):255-61. (PMID: 17261844) J Cell Biol. 2010 Jan 25;188(2):237-51. (PMID: 20083603) Front Cell Dev Biol. 2021 May 24;9:662711. (PMID: 34109175) Cell Host Microbe. 2009 Dec 17;6(6):551-62. (PMID: 20006843) PLoS Pathog. 2022 Jun 22;18(6):e1010643. (PMID: 35731833) Cell. 1997 Oct 17;91(2):253-62. (PMID: 9346242) Front Cell Dev Biol. 2016 Jan 26;4:1. (PMID: 26858948) Genes (Basel). 2018 Aug 08;9(8):. (PMID: 30096850) Autophagy. 2018;14(9):1649-1651. (PMID: 29973119) J Cell Sci. 2008 Jul 1;121(Pt 13):2123-9. (PMID: 18522993) NPJ Vaccines. 2021 Aug 10;6(1):98. (PMID: 34376691) Int J Parasitol. 2009 Mar;39(4):489-96. (PMID: 19000911) Int J Parasitol. 2007 Aug;37(10):1127-41. (PMID: 17428488) BMC Biol. 2014 Oct 30;12:86. (PMID: 25359557) Autophagy. 2014 Feb;10(2):269-84. (PMID: 24342964) Mol Microbiol. 2011 Jul;81(1):206-18. (PMID: 21542865) mBio. 2014 Jul 01;5(4):e01414-14. (PMID: 24987097) Mol Microbiol. 2016 Dec;102(5):775-791. (PMID: 27566438) J Cell Biol. 2001 Feb 5;152(3):595-606. (PMID: 11157985) Mol Microbiol. 2000 Nov;38(4):706-18. (PMID: 11115107) J Exp Med. 2003 Apr 21;197(8):1045-50. (PMID: 12707302) Methods Mol Biol. 2015;1325:81-9. (PMID: 26450381) Cell Microbiol. 2008 Jul;10(7):1505-16. (PMID: 18346224) J Cell Sci. 2001 Jun;114(Pt 12):2231-9. (PMID: 11493663) Int Immunopharmacol. 2024 May 10;132:111982. (PMID: 38569430) Cell Microbiol. 2011 Apr;13(4):569-86. (PMID: 21105984) Biochem J. 2011 Feb 1;433(3):423-33. (PMID: 21235525) J Proteome Res. 2019 Sep 6;18(9):3404-3418. (PMID: 31335145) Trends Parasitol. 2009 Feb;25(2):77-84. (PMID: 19101208) PLoS One. 2015 Sep 16;10(9):e0138626. (PMID: 26375591) FEBS Lett. 2009 Dec 3;583(23):3738-45. (PMID: 19837068) Science. 2006 Sep 1;313(5791):1287-90. (PMID: 16888102) Mol Biochem Parasitol. 1996 Dec 2;83(1):107-20. (PMID: 9010846) J Cell Biol. 2011 Dec 12;195(6):979-92. (PMID: 22144692) Parasitology. 2008 Jan;135(Pt 1):1-12. (PMID: 17908361) PLoS One. 2014 Feb 25;9(2):e89771. (PMID: 24587025) Cell Microbiol. 2009 Feb;11(2):279-88. (PMID: 19016774) Microsc Microanal. 2004 Oct;10(5):551-62. (PMID: 15525429) Malar J. 2019 Sep 24;18(1):330. (PMID: 31551073) Front Cell Dev Biol. 2016 Jan 06;3:84. (PMID: 26779480) Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10363-10368. (PMID: 30254161) Cell Microbiol. 2018 Aug;20(8):e12843. (PMID: 29579782) Cell. 2007 Aug 10;130(3):524-34. (PMID: 17655921) Dev Cell. 2018 Apr 23;45(2):245-261.e6. (PMID: 29689198) Comput Struct Biotechnol J. 2013 Aug 20;8:e201308002. (PMID: 24688742) mBio. 2016 Jun 28;7(3):. (PMID: 27353755) Eukaryot Cell. 2008 Jun;7(6):1062-70. (PMID: 18441124) Traffic. 2010 Nov;11(11):1391-400. (PMID: 21040294) PLoS Pathog. 2022 Sep 20;18(9):e1010846. (PMID: 36126089) J Cell Biol. 2005 Nov 21;171(4):587-92. (PMID: 16301328) Infect Immun. 2001 May;69(5):3286-94. (PMID: 11292751) J Cell Sci. 2005 Dec 1;118(Pt 23):5603-13. (PMID: 16306223) Biochim Biophys Acta. 1998 Aug 14;1404(1-2):259-70. (PMID: 9714825) Elife. 2016 Apr 26;5:. (PMID: 27115345) Amino Acids. 2011 Mar;40(3):847-56. (PMID: 20661758) Malar J. 2017 Nov 29;16(1):485. (PMID: 29187233) J Biol Chem. 2004 Mar 5;279(10):9490-6. (PMID: 14676185) Trends Parasitol. 2019 Jul;35(7):516-528. (PMID: 31147271) EMBO J. 1999 Sep 15;18(18):4949-60. (PMID: 10487747) Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14378-83. (PMID: 20660744) Cell Microbiol. 2019 May;21(5):e13018. (PMID: 30791192) FEBS Lett. 2000 Jul 28;478(1-2):137-40. (PMID: 10922485) Traffic. 2014 Apr;15(4):362-82. (PMID: 24423236) PLoS Pathog. 2021 Nov 8;17(11):e1010042. (PMID: 34748617) Mol Microbiol. 2008 Jun;68(6):1535-46. (PMID: 18410493) Science. 2004 Dec 10;306(5703):1930-3. (PMID: 15591202) Nat Protoc. 2006;1(1):346-56. (PMID: 17406255) Infect Immun. 1994 Nov;62(11):4844-7. (PMID: 7927764) Int J Parasitol. 2007 Oct;37(12):1329-41. (PMID: 17537443) Cell Res. 2010 Sep;20(9):1043-59. (PMID: 20567259) |
| Grant Information: | R21 AI117201 United States AI NIAID NIH HHS; R56 AI080631 United States AI NIAID NIH HHS; R56AI0806231 National Institute of Allergy and Infectious Diseases; R21AI117201 National Institute of Allergy and Infectious Diseases |
| Contributed Indexing: | Keywords: Golgi matrix protein GRASP; Plasmodium parasites; autophagy; liver form metamorphosis; micronemes |
| Substance Nomenclature: | 0 (Protozoan Proteins) 0 (Golgi Matrix Proteins) |
| Entry Date(s): | Date Created: 20250327 Date Completed: 20250611 Latest Revision: 20260721 |
| Update Code: | 20260722 |
| PubMed Central ID: | PMC12158648 |
| DOI: | 10.1111/mmi.15360 |
| PMID: | 40143578 |
| Βάση Δεδομένων: | MEDLINE |
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