TY  - JOUR
A1  - Dejung, Mario
A1  - Subota, Ines
A1  - Bucerius, Ferdinand
A1  - Dindar, Gülcin
A1  - Freiwald, Anja
A1  - Engstler, Markus
A1  - Boshart, Michael
A1  - Butter, Falk
A1  - Janzen, Chistian J.
T1  - Quantitative proteomics uncovers novel factors involved in developmental differentiation of Trypanosoma brucei
JF  - PLoS Pathogens
N2  - Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes.
KW  - cell differentiation
KW  - cell cycle and cell division
KW  - parasitic cell cycles
KW  - proteomes
KW  - chromatin
KW  - parasitic life cycles
KW  - transcriptome analysis
KW  - host-pathogen interactions
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146362
VL  - 12
IS  - 2
ER  - 
TY  - JOUR
A1  - Cicova, Zdenka
A1  - Dejung, Mario
A1  - Skalicky, Tomas
A1  - Eisenhuth, Nicole
A1  - Hanselmann, Steffen
A1  - Morriswood, Brooke
A1  - Figueiredo, Luisa M.
A1  - Butter, Falk
A1  - Janzen, Christian J.
T1  - Two flagellar BAR domain proteins in Trypanosoma brucei with stage-specific regulation
JF  - Scientific Reports
N2  - Trypanosomes are masters of adaptation to different host environments during their complex life cycle. Large-scale proteomic approaches provide information on changes at the cellular level, and in a systematic way. However, detailed work on single components is necessary to understand the adaptation mechanisms on a molecular level. Here, we have performed a detailed characterization of a bloodstream form (BSF) stage-specific putative flagellar host adaptation factor Tb927.11.2400, identified previously in a SILAC-based comparative proteome study. Tb927.11.2400 shares 38% amino acid identity with TbFlabarin (Tb927.11.2410), a procyclic form (PCF) stage-specific flagellar BAR domain protein. We named Tb927.11.2400 TbFlabarin-like (TbFlabarinL), and demonstrate that it originates from a gene duplication event, which occurred in the African trypanosomes. TbFlabarinL is not essential for the growth of the parasites under cell culture conditions and it is dispensable for developmental differentiation from BSF to the PCF in vitro. We generated TbFlabarinL-specific antibodies, and showed that it localizes in the flagellum. Co-immunoprecipitation experiments together with a biochemical cell fractionation suggest a dual association of TbFlabarinL with the flagellar membrane and the components of the paraflagellar rod.
KW  - parasite biology
KW  - protein translocation
KW  - Trypanosoma brucei
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181021
VL  - 6
ER  -