chaperone requirements for biosynthesis of the trypanosome variant surface glycoprotein锥体虫变异的伴侣要求生物合成表面糖蛋白.pdfVIP

Chaperone Requirements for Biosynthesis of the Trypanosome Variant Surface Glycoprotein 1 1 1,2 ¨ 1 3 Mark C. Field *, Tatiana Sergeenko , Ya-Nan Wang , Susanne Bohm , Mark Carrington 1 Department of Pathology, University of Cambridge, Cambridge, United Kingdom, 2 College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China, 3 Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom Abstract Background: Trypanosoma brucei does not respond transcriptionally to several endoplasmic reticulum (ER) stress conditions, including tunicamycin or dithiothreitol, indicating the absence of a conventional unfolded protein response. This suggests divergent mechanisms for quality control (QC) of ER protein folding and export may be present in trypanosomes. As the variant surface glycoprotein (VSG) represents ,90% of trypanosome plasma membrane protein, it is possible that VSG has evolved to fold efficiently to minimize ER folding burden. Methodology/Principal Findings: We demonstrate the presence of a QC system by pharmacological inhibition of the trypanosome 26S proteasome. This indicates active proteasome-mediated VSG turnover as ,2.5 fold more VSG is recovered from cell lysates following MG132 inhibition. An in silico scan of the trypanosome genome identified 28 open reading frames likely to encode polypeptides participating in ER nascent chain maturation. By RNA interference we monitored the importance of these gene products to proliferation, VSG abundance and cell morphology. 68% of the cohort were required for normal proli