TY  - JOUR
A1  - Link, Fabian
A1  - Borges, Alyssa R.
A1  - Jones, Nicola G.
A1  - Engstler, Markus
T1  - To the Surface and Back: Exo- and Endocytic Pathways in Trypanosoma brucei
JF  - Frontiers in Cell and Developmental Biology
N2  - Trypanosoma brucei is one of only a few unicellular pathogens that thrives extracellularly in the vertebrate host. Consequently, the cell surface plays a critical role in both immune recognition and immune evasion. The variant surface glycoprotein (VSG) coats the entire surface of the parasite and acts as a flexible shield to protect invariant proteins against immune recognition. Antigenic variation of the VSG coat is the major virulence mechanism of trypanosomes. In addition, incessant motility of the parasite contributes to its immune evasion, as the resulting fluid flow on the cell surface drags immunocomplexes toward the flagellar pocket, where they are internalized. The flagellar pocket is the sole site of endo- and exocytosis in this organism. After internalization, VSG is rapidly recycled back to the surface, whereas host antibodies are thought to be transported to the lysosome for degradation. For this essential step to work, effective machineries for both sorting and recycling of VSGs must have evolved in trypanosomes. Our understanding of the mechanisms behind VSG recycling and VSG secretion, is by far not complete. This review provides an overview of the trypanosome secretory and endosomal pathways. Longstanding questions are pinpointed that, with the advent of novel technologies, might be answered in the near future.
KW  - cell surface
KW  - African trypanosomes
KW  - endocytosis
KW  - exocytosis
KW  - membrane recycling
KW  - Rab
KW  - clathrin
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244682
SN  - 2296-634X
VL  - 9
ER  - 
TY  - JOUR
A1  - Harrington, John M.
A1  - Scelsi, Chris
A1  - Hartel, Andreas
A1  - Jones, Nicola G.
A1  - Engstler, Markus
A1  - Capewell, Paul
A1  - MacLeod, Annette
A1  - Hajduk, Stephen
T1  - Novel African Trypanocidal Agents: Membrane Rigidifying Peptides
JF  - PLoS One
N2  - The bloodstream developmental forms of pathogenic African trypanosomes are uniquely susceptible to killing by small hydrophobic peptides. Trypanocidal activity is conferred by peptide hydrophobicity and charge distribution and results from increased rigidity of the plasma membrane. Structural analysis of lipid-associated peptide suggests a mechanism of phospholipid clamping in which an internal hydrophobic bulge anchors the peptide in the membrane and positively charged moieties at the termini coordinate phosphates of the polar lipid headgroups. This mechanism reveals a necessary phenotype in bloodstream form African trypanosomes, high membrane fluidity, and we suggest that targeting the plasma membrane lipid bilayer as a whole may be a novel strategy for the development of new pharmaceutical agents. Additionally, the peptides we have described may be valuable tools for probing the biosynthetic machinery responsible for the unique composition and characteristics of African trypanosome plasma membranes.
KW  - depth
KW  - trypanosome lytic factor
KW  - signal peptides
KW  - cell surface
KW  - protein
KW  - brucei
KW  - environment
KW  - bilayers
KW  - binding
KW  - probes
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135179
VL  - 7
IS  - 9
ER  -