TY  - JOUR
A1  - Hartel, Andreas J.W.
A1  - Glogger, Marius
A1  - Jones, Nicola G.
A1  - Abuillan, Wasim
A1  - Batram, Christopher
A1  - Hermann, Anne
A1  - Fenz, Susanne F.
A1  - Tanaka, Motomu
A1  - Engstler, Markus
T1  - N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold
JF  - Nature Communications
N2  - The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. The diversity of the membrane proteome of most cells may preclude systematic studies. African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. Obstacles in the form of heterologous proteins compromise the diffusion coefficient and the MCT. The trypanosome VSG-coat operates very close to its MCT. Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed.
KW  - parasitology
KW  - cellular imaging
KW  - membrane biophysics
KW  - single-molecule biophysics
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171368
VL  - 7
ER  - 
TY  - JOUR
A1  - Batram, Christopher
A1  - Jones, Nivola G.
A1  - Janzen, Christian J.
A1  - Markert, Sebastian M.
A1  - Engstler, Markus
T1  - Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei
JF  - eLife
N2  - We have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. Three conserved expression-site-associated genes (ESAGs) appear to serve as signal for ES attenuation. Their depletion causes G1-phase dormancy and reversible initiation of the slender-to-stumpy differentiation pathway. ES-attenuated slender bloodstream trypanosomes gain full developmental competence for transformation to the tsetse fly stage. This surprising connection between antigenic variation and developmental progression provides an unexpected point of attack against the deadly sleeping sickness.
KW  - antigenic variation
KW  - expression site attenuation
KW  - developmental reprogramming
KW  - cell biology
KW  - genes and chromosomes
KW  - Trypanosoma brucei
KW  - variant surface glycoprotein (VSG)
KW  - monoallelic expression
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119727
SN  - 2050-084X
VL  - 3
IS  - e02324
ER  - 
TY  - JOUR
A1  - Zimmermann, Henriette
A1  - Subota, Ines
A1  - Batram, Christopher
A1  - Kramer, Susanne
A1  - Janzen, Christian J.
A1  - Jones, Nicola G.
A1  - Engstler, Markus
T1  - A quorum sensing-independent path to stumpy development in Trypanosoma brucei
JF  - PLoS Pathogens
N2  - For persistent infections of the mammalian host, African trypanosomes limit their population size by quorum sensing of the parasite-excreted stumpy induction factor (SIF), which induces development to the tsetse-infective stumpy stage. We found that besides this cell density-dependent mechanism, there exists a second path to the stumpy stage that is linked to antigenic variation, the main instrument of parasite virulence. The expression of a second variant surface glycoprotein (VSG) leads to transcriptional attenuation of the VSG expression site (ES) and immediate development to tsetse fly infective stumpy parasites. This path is independent of SIF and solely controlled by the transcriptional status of the ES. In pleomorphic trypanosomes varying degrees of ES-attenuation result in phenotypic plasticity. While full ES-attenuation causes irreversible stumpy development, milder attenuation may open a time window for rescuing an unsuccessful antigenic switch, a scenario that so far has not been considered as important for parasite survival.
KW  - Trypanosoma
KW  - hyperexpression techniques
KW  - parasitic cell cycles
KW  - cloning
KW  - cell cycle and cell division
KW  - cell differentiation
KW  - tetracyclines
KW  - parasitic diseases
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158230
VL  - 13
IS  - 4
ER  -