Internal and surface-localized major surface proteases of Leishmania spp. and their differential release from promastigotes

Chaoqun Yao; John E Donelson; Mary E Wilson

doi:10.1128/EC.00073-07

Back

Internal and surface-localized major surface proteases of Leishmania spp. and their differential release from promastigotes

Journal article

Open access

Peer reviewed

Internal and surface-localized major surface proteases of Leishmania spp. and their differential release from promastigotes

Chaoqun Yao, John E Donelson and Mary E Wilson

Eukaryotic cell, Vol.6(10), pp.1905-1912

10/2007

DOI: 10.1128/EC.00073-07

PMCID: PMC2043387

PMID: 17693594

Files and links (1)

url

https://doi.org/10.1128/EC.00073-07View

Published (Version of record) Open Access

Abstract

Major surface protease (MSP), also called GP63, is a virulence factor of Leishmania spp. protozoa. There are three pools of MSP, located either internally within the parasite, anchored to the surface membrane, or released into the extracellular environment. The regulation and biological functions of these MSP pools are unknown. We investigated here the trafficking and extrusion of surface versus internal MSPs. Virulent Leishmania chagasi undergo a growth-associated lengthening in the t(1/2) of surface-localized MSP, but this did not occur in the attenuated L5 strain. The release of surface-localized MSP was enhanced in a dose-dependent manner by MbetaCD, which chelates membrane cholesterol-ergosterol. Furthermore, incubation of promastigotes at 37 degrees C with Matrigel matrix, a soluble basement membrane extract of Engelbreth-Holm-Swarm tumor cells, stimulated the release of internal MSP but not of surface-located MSP. Taken together, these data indicate that MSP subpopulations in distinct cellular locations are released from the parasite under different environmental conditions. We hypothesize that the internal MSP with its lengthy t(1/2) does not serve as a pool for promastigote surface MSP in the sand fly vector but that it instead functions as an MSP pool ready for quick release upon inoculation of metacyclic promastigotes into mammals. We present a model in which these different MSP pools are released under distinct life cycle-specific conditions.

Virulence - drug effects

Cricetinae

Temperature

Proteoglycans

Peptide Hydrolases - secretion

beta-Cyclodextrins - pharmacology

Isoenzymes - secretion

Dose-Response Relationship, Drug

Leishmania - cytology

Animals

Laminin

Leishmania - enzymology

Models, Biological

Collagen

Clone Cells

Leishmania - pathogenicity

Drug Combinations

Details

Title: Subtitle: Internal and surface-localized major surface proteases of Leishmania spp. and their differential release from promastigotes
Creators: Chaoqun Yao - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. chaoqun-yao@uiowa.edu
John E Donelson
Mary E Wilson
Resource Type: Journal article
Publication Details: Eukaryotic cell, Vol.6(10), pp.1905-1912
DOI: 10.1128/EC.00073-07
PMID: 17693594
PMCID: PMC2043387
NLM abbreviation: Eukaryot Cell
ISSN: 1535-9778
eISSN: 1535-9786
Publisher: American Society for Microbiology; United States
Grant note: R21 AI032135 / NIAID NIH HHS R01 AI045540 / NIAID NIH HHS R01 AI032135 / NIAID NIH HHS R01 AI32135 / NIAID NIH HHS R01 AI059451 / NIAID NIH HHS R01 AI067874 / NIAID NIH HHS R01 AI048822 / NIAID NIH HHS
Language: English
Date published: 10/2007
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984001140902771

Metrics

23 Record Views

22 Times Cited - Web of Science