Proteins with glycosylphosphatidylinositol (GPI) signal sequences have divergent fates during a GPI deficiency. GPIs are essential for nuclear division in Trypanosoma cruzi

Nisha Garg, Rick L. Tarleton, Kojo Mensa-Wilmot

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Glycosylphosphatidylinositols (GPIs) are membrane anchors for cell surface proteins of several major protozoan parasites of humans, including Trypanosoma cruzi, the causative agent of Chagas' disease. To investigate the general role of GPIs in T. cruzi, we generated GPI-deficient parasites by heterologous expression of T. brucei GPI-phospholipase C. Putative protein- GPI inter mediates were depleted, causing the biochemical equivalent of a dominant-negative loss of function mutation in the GPI pathway. Cell surface expression of major GPI-anchored proteins was diminished in GPI-deficient T. cruzi. Four proteins that are normally GPI-anchored in T. cruzi exhibited different fates during the GPI shortage; Ssp-4 and p75 were secreted prematurely, while protease gp50/55 and p60 were degraded intracellularly. These observations demonstrate that secretion and intracellular degradation of GPI-anchored proteins may occur in the same genetic background during a GPI deficiency. We postulate that the interaction between a protein-GPI transamidase and the COOH-terminal GPI signal sequence plays a pivotal role in determining the fate of these proteins. At a nonpermissive GPI deficiency, T. cruzi amastigotes inside mammalian cells replicated their single kinetoplast but failed at mitosis. Hence, in these protozoans, GPIs appear to be essential for nuclear division, but not for mitochondrial duplication.

Original languageEnglish (US)
Pages (from-to)12482-12491
Number of pages10
JournalJournal of Biological Chemistry
Volume272
Issue number19
DOIs
StatePublished - May 9 1997
Externally publishedYes

Fingerprint

Cell Nucleus Division
Glycosylphosphatidylinositols
Trypanosoma cruzi
Protein Sorting Signals
Proteins
Glycosylphosphatidylinositol deficiency
Parasites
Chagas Disease
Type C Phospholipases
Mitosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Proteins with glycosylphosphatidylinositol (GPI) signal sequences have divergent fates during a GPI deficiency. GPIs are essential for nuclear division in Trypanosoma cruzi. / Garg, Nisha; Tarleton, Rick L.; Mensa-Wilmot, Kojo.

In: Journal of Biological Chemistry, Vol. 272, No. 19, 09.05.1997, p. 12482-12491.

Research output: Contribution to journalArticle

@article{de51209d0b1f4d6a8e1993ffd8ccf3f7,
title = "Proteins with glycosylphosphatidylinositol (GPI) signal sequences have divergent fates during a GPI deficiency. GPIs are essential for nuclear division in Trypanosoma cruzi",
abstract = "Glycosylphosphatidylinositols (GPIs) are membrane anchors for cell surface proteins of several major protozoan parasites of humans, including Trypanosoma cruzi, the causative agent of Chagas' disease. To investigate the general role of GPIs in T. cruzi, we generated GPI-deficient parasites by heterologous expression of T. brucei GPI-phospholipase C. Putative protein- GPI inter mediates were depleted, causing the biochemical equivalent of a dominant-negative loss of function mutation in the GPI pathway. Cell surface expression of major GPI-anchored proteins was diminished in GPI-deficient T. cruzi. Four proteins that are normally GPI-anchored in T. cruzi exhibited different fates during the GPI shortage; Ssp-4 and p75 were secreted prematurely, while protease gp50/55 and p60 were degraded intracellularly. These observations demonstrate that secretion and intracellular degradation of GPI-anchored proteins may occur in the same genetic background during a GPI deficiency. We postulate that the interaction between a protein-GPI transamidase and the COOH-terminal GPI signal sequence plays a pivotal role in determining the fate of these proteins. At a nonpermissive GPI deficiency, T. cruzi amastigotes inside mammalian cells replicated their single kinetoplast but failed at mitosis. Hence, in these protozoans, GPIs appear to be essential for nuclear division, but not for mitochondrial duplication.",
author = "Nisha Garg and Tarleton, {Rick L.} and Kojo Mensa-Wilmot",
year = "1997",
month = "5",
day = "9",
doi = "10.1074/jbc.272.19.12482",
language = "English (US)",
volume = "272",
pages = "12482--12491",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "19",

}

TY - JOUR

T1 - Proteins with glycosylphosphatidylinositol (GPI) signal sequences have divergent fates during a GPI deficiency. GPIs are essential for nuclear division in Trypanosoma cruzi

AU - Garg, Nisha

AU - Tarleton, Rick L.

AU - Mensa-Wilmot, Kojo

PY - 1997/5/9

Y1 - 1997/5/9

N2 - Glycosylphosphatidylinositols (GPIs) are membrane anchors for cell surface proteins of several major protozoan parasites of humans, including Trypanosoma cruzi, the causative agent of Chagas' disease. To investigate the general role of GPIs in T. cruzi, we generated GPI-deficient parasites by heterologous expression of T. brucei GPI-phospholipase C. Putative protein- GPI inter mediates were depleted, causing the biochemical equivalent of a dominant-negative loss of function mutation in the GPI pathway. Cell surface expression of major GPI-anchored proteins was diminished in GPI-deficient T. cruzi. Four proteins that are normally GPI-anchored in T. cruzi exhibited different fates during the GPI shortage; Ssp-4 and p75 were secreted prematurely, while protease gp50/55 and p60 were degraded intracellularly. These observations demonstrate that secretion and intracellular degradation of GPI-anchored proteins may occur in the same genetic background during a GPI deficiency. We postulate that the interaction between a protein-GPI transamidase and the COOH-terminal GPI signal sequence plays a pivotal role in determining the fate of these proteins. At a nonpermissive GPI deficiency, T. cruzi amastigotes inside mammalian cells replicated their single kinetoplast but failed at mitosis. Hence, in these protozoans, GPIs appear to be essential for nuclear division, but not for mitochondrial duplication.

AB - Glycosylphosphatidylinositols (GPIs) are membrane anchors for cell surface proteins of several major protozoan parasites of humans, including Trypanosoma cruzi, the causative agent of Chagas' disease. To investigate the general role of GPIs in T. cruzi, we generated GPI-deficient parasites by heterologous expression of T. brucei GPI-phospholipase C. Putative protein- GPI inter mediates were depleted, causing the biochemical equivalent of a dominant-negative loss of function mutation in the GPI pathway. Cell surface expression of major GPI-anchored proteins was diminished in GPI-deficient T. cruzi. Four proteins that are normally GPI-anchored in T. cruzi exhibited different fates during the GPI shortage; Ssp-4 and p75 were secreted prematurely, while protease gp50/55 and p60 were degraded intracellularly. These observations demonstrate that secretion and intracellular degradation of GPI-anchored proteins may occur in the same genetic background during a GPI deficiency. We postulate that the interaction between a protein-GPI transamidase and the COOH-terminal GPI signal sequence plays a pivotal role in determining the fate of these proteins. At a nonpermissive GPI deficiency, T. cruzi amastigotes inside mammalian cells replicated their single kinetoplast but failed at mitosis. Hence, in these protozoans, GPIs appear to be essential for nuclear division, but not for mitochondrial duplication.

UR - http://www.scopus.com/inward/record.url?scp=0030911733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030911733&partnerID=8YFLogxK

U2 - 10.1074/jbc.272.19.12482

DO - 10.1074/jbc.272.19.12482

M3 - Article

VL - 272

SP - 12482

EP - 12491

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 19

ER -