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Proteomics on the rims: insights into the biology of the nuclear envelope and flagellar pocket of trypanosomes

Published online by Cambridge University Press:  06 February 2012

MARK C. FIELD ,
VINCENT ADUNG'A ,
SAMSON OBADO ,
BRIAN T. CHAIT  and
MICHAEL P. ROUT
MARK C. FIELD*
Affiliation:
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK
VINCENT ADUNG'A
Affiliation:
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK
SAMSON OBADO
Affiliation:
Laboratories of Cellular and Structural Biology, The Rockefeller University, New York, USA
BRIAN T. CHAIT
Affiliation:
Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, USA
MICHAEL P. ROUT
Affiliation:
Laboratories of Cellular and Structural Biology, The Rockefeller University, New York, USA
*
*Corresponding author: Phone: +44 (0)751-550-7880. E-mail: [email protected]
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Summary

Trypanosomatids represent the causative agents of major diseases in humans, livestock and plants, with inevitable suffering and economic hardship as a result. They are also evolutionarily highly divergent organisms, and the many unique aspects of trypanosome biology provide opportunities in terms of identification of drug targets, the challenge of exploiting these putative targets and, at the same time, significant scope for exploration of novel and divergent cell biology. We can estimate from genome sequences that the degree of divergence of trypanosomes from animals and fungi is extreme, with perhaps one third to one half of predicted trypanosome proteins having no known function based on homology or recognizable protein domains/architecture. Two highly important aspects of trypanosome biology are the flagellar pocket and the nuclear envelope, where in silico analysis clearly suggests great potential divergence in the proteome. The flagellar pocket is the sole site of endo- and exocytosis in trypanosomes and plays important roles in immune evasion via variant surface glycoprotein (VSG) trafficking and providing a location for sequestration of various invariant receptors. The trypanosome nuclear envelope has been largely unexplored but, by analogy with higher eukaryotes, roles in the regulation of chromatin and most significantly, in controlling VSG gene expression are expected. Here we discuss recent successful proteomics-based approaches towards characterization of the nuclear envelope and the endocytic apparatus, the identification of conserved and novel trypanosomatid-specific features, and the implications of these findings.

Keywords

Proteomicsnuclear pore complexflagellar pocketsystems biologymolecular evolutionprotein complexprotein interactions
Type
Research Article
Information
Parasitology , Volume 139 , Issue 9: Symposia of the British Society for Parasitology Volume 48 Proteomic insights into parasite biology , August 2012 , pp. 1158 - 1167
Copyright
Copyright © Cambridge University Press 2012

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