دورية أكاديمية
أعرض في EDS

Trypanosoma brucei Pex13.2 Is an Accessory Peroxin That Functions in the Import of Peroxisome Targeting Sequence Type 2 Proteins and Localizes to Subdomains of the Glycosome.

التفاصيل البيبلوغرافية
العنوان: Trypanosoma brucei Pex13.2 Is an Accessory Peroxin That Functions in the Import of Peroxisome Targeting Sequence Type 2 Proteins and Localizes to Subdomains of the Glycosome.
المؤلفون: Crowe LP; Eukaryotic Innovations Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA., Wilkinson CL; Eukaryotic Innovations Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA., Nicholson KR; Eukaryotic Innovations Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA., Morris MT; Eukaryotic Innovations Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA mmorri3@clemson.edu.
المصدر: MSphere [mSphere] 2020 Feb 19; Vol. 5 (1). Date of Electronic Publication: 2020 Feb 19.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101674533 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-5042 (Electronic) Linking ISSN: 23795042 NLM ISO Abbreviation: mSphere Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society for Microbiology, [2015]-
مواضيع طبية MeSH: Microbodies/*metabolism , Peroxins/*metabolism , Peroxisomes/*metabolism , Protozoan Proteins/*metabolism , Trypanosoma brucei brucei/*genetics, Cytosol/chemistry ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Peroxins/genetics ; Peroxisomes/genetics ; Protein Transport ; Protozoan Proteins/genetics
مستخلص: Kinetoplastid parasites, including Trypanosoma brucei , Trypanosoma cruzi , and Leishmania , harbor unique organelles known as glycosomes, which are evolutionarily related to peroxisomes. Glycosome/peroxisome biogenesis is mediated by proteins called peroxins that facilitate organelle formation, proliferation, and degradation and import of proteins housed therein. Import of matrix proteins occurs via one of two pathways that are dictated by their peroxisome targeting sequence (PTS). In PTS1 import, a C-terminal tripeptide sequence, most commonly SKL, is recognized by the soluble receptor Pex5. In PTS2 import, a less conserved N-terminal sequence is recognized by Pex7. The soluble receptors deliver their cargo to the import channel consisting minimally of Pex13 and Pex14. While much of the import process is conserved, kinetoplastids are the only organisms to have two Pex13s, Pex13.1 and Pex13.2. It is unclear why trypanosomes require two Pex13s when one is sufficient for most eukaryotes. To interrogate the role of Pex13.2, we have employed biochemical approaches to partially resolve the composition of the Pex13/Pex14 import complexes in T. brucei and characterized glycosome morphology and protein import in Pex13.2-deficient parasites. Here, we show that Pex13.2 is an integral glycosome membrane protein that interacts with Pex13.1 and Pex14. The N terminus of Pex13.2 faces the cytoplasmic side of the membrane, where it can facilitate interactions required for protein import. Two-dimensional gel electrophoresis revealed three glycosome membrane complexes containing combinations of Pex13.1, Pex13.2, and Pex14. The silencing of Pex13.2 resulted in parasites with fewer, larger glycosomes and disrupted glycosome protein import, suggesting the protein is involved in glycosome biogenesis as well as protein import. Furthermore, superresolution microscopy demonstrated that Pex13.2 localizes to discrete foci in the glycosome periphery, indicating that the glycosome periphery is not homogenous. IMPORTANCE Trypanosoma brucei causes human African trypanosomiasis and a wasting disease called Nagana in livestock. Current treatments are expensive, toxic, and difficult to administer. Because of this, the search for new drug targets is essential. T. brucei has glycosomes that are essential to parasite survival; however, our ability to target them in drug development is hindered by our lack of understanding about how these organelles are formed and maintained. This work forwards our understanding of how the parasite-specific protein Pex13.2 functions in glycosome protein import and lays the foundation for future studies focused on blocking Pex13.2 function, which would be lethal to bloodstream-form parasites that reside in the mammalian bloodstream.
(Copyright © 2020 Crowe et al.)
References: FEMS Microbiol Rev. 2004 Nov;28(5):603-43. (PMID: 15539076)
Eukaryot Cell. 2013 Aug;12(8):1072-9. (PMID: 23709182)
J Mol Biol. 2015 Mar 27;427(6 Pt A):1176-90. (PMID: 25681696)
Biochim Biophys Acta. 2006 Dec;1763(12):1585-91. (PMID: 17056133)
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17718-23. (PMID: 19008351)
Acta Histochem Cytochem. 2007 Aug 30;40(4):101-11. (PMID: 17898874)
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14177-82. (PMID: 12386344)
Nat Methods. 2012 Jul;9(7):671-5. (PMID: 22930834)
FEBS J. 2019 Jan;286(1):205-222. (PMID: 30414318)
Microb Cell. 2017 Jul 03;4(7):229-232. (PMID: 28706938)
Biochem Biophys Res Commun. 2012 Aug 10;424(4):781-5. (PMID: 22809509)
J Cell Biol. 1987 Dec;105(6 Pt 1):2649-54. (PMID: 3320052)
J Biol Chem. 2000 Dec 22;275(51):40174-9. (PMID: 11013266)
J Biol Chem. 2016 Aug 12;291(33):16948-62. (PMID: 27311714)
Science. 1995 May 26;268(5214):1179-83. (PMID: 7761835)
Mol Cell Biol. 2000 Oct;20(20):7516-26. (PMID: 11003648)
FEBS Lett. 2012 Jun 21;586(13):1765-71. (PMID: 22641036)
Nat Methods. 2012 Jun 28;9(7):676-82. (PMID: 22743772)
Biochim Biophys Acta. 2009 Mar;1793(3):516-27. (PMID: 19185591)
Biochim Biophys Acta. 2007 Apr;1773(4):521-35. (PMID: 17320990)
mSphere. 2018 Oct 31;3(5):. (PMID: 30381351)
Biochim Biophys Acta. 2012 Jul;1823(7):1133-41. (PMID: 22546606)
Autophagy. 2008 Apr;4(3):294-308. (PMID: 18365344)
EMBO J. 1996 Jun 17;15(12):2901-13. (PMID: 8670791)
Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2087-92. (PMID: 10681445)
J Biol Chem. 2001 Aug 10;276(32):29935-42. (PMID: 11397814)
J Mol Biol. 2001 Jan 19;305(3):567-80. (PMID: 11152613)
J Biol Chem. 1996 Aug 2;271(31):18387-93. (PMID: 8702482)
J Cell Biol. 1993 Feb;120(3):665-73. (PMID: 8425895)
Nat Rev Mol Cell Biol. 2013 Dec;14(12):803-17. (PMID: 24263361)
Proteomics. 2006 Jun;6(11):3275-93. (PMID: 16622829)
EMBO J. 1998 Jul 1;17(13):3542-55. (PMID: 9649425)
Mol Biochem Parasitol. 2001 Jun;115(1):19-28. (PMID: 11377736)
J Cell Biol. 1989 May;108(5):1657-64. (PMID: 2654139)
Eukaryot Cell. 2007 Aug;6(8):1439-49. (PMID: 17586720)
J Microsc. 1993 Mar;169(3):375-382. (PMID: 33930978)
معلومات مُعتمدة: P20 GM109094 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Pex13; Trypanosoma brucei; glycosome; kinetoplastids; parasites; peroxisome
المشرفين على المادة: 0 (Membrane Proteins)
0 (Peroxins)
0 (Protozoan Proteins)
تواريخ الأحداث: Date Created: 20200221 Date Completed: 20201124 Latest Revision: 20240328
رمز التحديث: 20240329
مُعرف محوري في PubMed: PMC7031615
DOI: 10.1128/mSphere.00744-19
PMID: 32075879
قاعدة البيانات: MEDLINE
الوصف
تدمد:2379-5042
DOI:10.1128/mSphere.00744-19