Novel structural components of the ventral disc and lateral crest in Giardia intestinalis.
Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis, one of the most common protozoan diarrheal diseases in the world. Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure, the ventral disc. Surr...
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ftdoajarticles:oai:doaj.org/article:63837b4b15dd4967893aefd3819d275b 2023-05-15T15:11:37+02:00 Novel structural components of the ventral disc and lateral crest in Giardia intestinalis. Kari D Hagen Matthew P Hirakawa Susan A House Cindi L Schwartz Jonathan K Pham Michael J Cipriano Moises J De La Torre Albert C Sek Gary Du Brystal M Forsythe Scott C Dawson 2011-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001442 https://doaj.org/article/63837b4b15dd4967893aefd3819d275b EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3243723?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001442 https://doaj.org/article/63837b4b15dd4967893aefd3819d275b PLoS Neglected Tropical Diseases, Vol 5, Iss 12, p e1442 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001442 2022-12-31T05:57:09Z Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis, one of the most common protozoan diarrheal diseases in the world. Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure, the ventral disc. Surrounding the ventral disc is a less characterized putatively contractile structure, the lateral crest, which forms a continuous perimeter seal with the substrate. A better understanding of ventral disc and lateral crest structure, conformational dynamics, and biogenesis is critical for understanding the mechanism of giardial attachment to the host. To determine the components comprising the ventral disc and lateral crest, we used shotgun proteomics to identify proteins in a preparation of isolated ventral discs. Candidate disc-associated proteins, or DAPs, were GFP-tagged using a ligation-independent high-throughput cloning method. Based on disc localization, we identified eighteen novel DAPs, which more than doubles the number of known disc-associated proteins. Ten of the novel DAPs are associated with the lateral crest or outer edge of the disc, and are the first confirmed components of this structure. Using Fluorescence Recovery After Photobleaching (FRAP) with representative novel DAP::GFP strains we found that the newly identified DAPs tested did not recover after photobleaching and are therefore structural components of the ventral disc or lateral crest. Functional analyses of the novel DAPs will be central toward understanding the mechanism of ventral disc-mediated attachment and the mechanism of disc biogenesis during cell division. Since attachment of Giardia to the intestine via the ventral disc is essential for pathogenesis, it is possible that some proteins comprising the disc could be potential drug targets if their loss or disruption interfered with disc biogenesis or function, preventing attachment. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 12 e1442 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Kari D Hagen Matthew P Hirakawa Susan A House Cindi L Schwartz Jonathan K Pham Michael J Cipriano Moises J De La Torre Albert C Sek Gary Du Brystal M Forsythe Scott C Dawson Novel structural components of the ventral disc and lateral crest in Giardia intestinalis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis, one of the most common protozoan diarrheal diseases in the world. Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure, the ventral disc. Surrounding the ventral disc is a less characterized putatively contractile structure, the lateral crest, which forms a continuous perimeter seal with the substrate. A better understanding of ventral disc and lateral crest structure, conformational dynamics, and biogenesis is critical for understanding the mechanism of giardial attachment to the host. To determine the components comprising the ventral disc and lateral crest, we used shotgun proteomics to identify proteins in a preparation of isolated ventral discs. Candidate disc-associated proteins, or DAPs, were GFP-tagged using a ligation-independent high-throughput cloning method. Based on disc localization, we identified eighteen novel DAPs, which more than doubles the number of known disc-associated proteins. Ten of the novel DAPs are associated with the lateral crest or outer edge of the disc, and are the first confirmed components of this structure. Using Fluorescence Recovery After Photobleaching (FRAP) with representative novel DAP::GFP strains we found that the newly identified DAPs tested did not recover after photobleaching and are therefore structural components of the ventral disc or lateral crest. Functional analyses of the novel DAPs will be central toward understanding the mechanism of ventral disc-mediated attachment and the mechanism of disc biogenesis during cell division. Since attachment of Giardia to the intestine via the ventral disc is essential for pathogenesis, it is possible that some proteins comprising the disc could be potential drug targets if their loss or disruption interfered with disc biogenesis or function, preventing attachment. |
format |
Article in Journal/Newspaper |
author |
Kari D Hagen Matthew P Hirakawa Susan A House Cindi L Schwartz Jonathan K Pham Michael J Cipriano Moises J De La Torre Albert C Sek Gary Du Brystal M Forsythe Scott C Dawson |
author_facet |
Kari D Hagen Matthew P Hirakawa Susan A House Cindi L Schwartz Jonathan K Pham Michael J Cipriano Moises J De La Torre Albert C Sek Gary Du Brystal M Forsythe Scott C Dawson |
author_sort |
Kari D Hagen |
title |
Novel structural components of the ventral disc and lateral crest in Giardia intestinalis. |
title_short |
Novel structural components of the ventral disc and lateral crest in Giardia intestinalis. |
title_full |
Novel structural components of the ventral disc and lateral crest in Giardia intestinalis. |
title_fullStr |
Novel structural components of the ventral disc and lateral crest in Giardia intestinalis. |
title_full_unstemmed |
Novel structural components of the ventral disc and lateral crest in Giardia intestinalis. |
title_sort |
novel structural components of the ventral disc and lateral crest in giardia intestinalis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001442 https://doaj.org/article/63837b4b15dd4967893aefd3819d275b |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 12, p e1442 (2011) |
op_relation |
http://europepmc.org/articles/PMC3243723?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001442 https://doaj.org/article/63837b4b15dd4967893aefd3819d275b |
op_doi |
https://doi.org/10.1371/journal.pntd.0001442 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
5 |
container_issue |
12 |
container_start_page |
e1442 |
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1766342448550772736 |