Cell homeostasis in a Leishmania major mutant overexpressing the spliced leader RNA is maintained by an increased proteolytic activity

Autor(es)

Toledo, Juliano S. ^[1] ; Ferreira, Tiago R. ^[1] ; Defina, Tania P. A. ^[1] ; Dossin, Fernando de M. ^[2] ; Beattie, Kenneth A. ^[3] ; Lamont, Douglas J. ^[3] ; Cloutier, Serge ^[4] ; Papadopoulou, Barbara ^[4] ; Schenkman, Sergio ^[5] ; Cruz, Angela K. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Sao Paulo - Brazil

^[2] Inst Pasteur Korea, Ctr Neglected Dis Drug Discovery CND3, Seoul - South Korea

^[3] Univ Dundee, Coll Life Sci, Fingerprints Prote Facil, Dundee - Scotland

^[4] Univ Laval, CHU Laval, Ctr Rech Infectiol, Quebec City, PQ - Canada

^[5] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY; v. 42, n. 10, p. 1661-1671, OCT 2010.
• Citações Web of Science: 4

Resumo

Although several stage-specific genes have been identified in Leishmania, the molecular mechanisms governing developmental gene regulation in this organism are still not well understood. We have previously reported an attenuation of virulence in Leishmania major and L braziliensis carrying extra-copies of the spliced leader RNA gene. Here, we surveyed the major differences in proteome and transcript expression profiles between the spliced leader RNA overexpressor and control lines using two-dimensional gel electrophoresis and differential display reverse transcription PCR, respectively. Thirty-nine genes related to stress response, cytoskeleton, proteolysis, cell cycle control and proliferation, energy generation, gene transcription, RNA processing and post-transcriptional regulation have abnormal patterns of expression in the spliced leader RNA overexpressor line. The evaluation of proteolytic pathways in the mutant revealed a selective increase of cysteine protease activity and an exacerbated ubiquitin-labeled protein population. Polysome profile analysis and measurement of cellular protein aggregates showed that protein translation in the spliced leader RNA overexpressor line is increased when compared to the control line. We found that L major promastigotes maintain homeostasis in culture when challenged with a metabolic imbalance generated by spliced leader RNA surplus through modulation of intracellular proteolysis. However, this might interfere with a fine-tuned gene expression control necessary for the amastigote multiplication in the mammalian host. (c) 2010 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 07/06443-0 - Investigação da atividade de vias proteolíticas em mutantes de Leishmania superexpressores de miniexon.
• Beneficiário: Tiago Rodrigues Ferreira
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 03/02366-0 - Miniexon e virulencia em leishmania major.
• Beneficiário: Juliano Simões de Toledo
• Modalidade de apoio: Bolsas no Brasil - Doutorado