Vergleichende Charakterisierung einer auf Alveolaten beschränkten Proteinfamilie, den "Inner Membrane Complex" Proteinen

• Applicant: Professor Dr. Sven B. Gould
• Subject Area: Cell Biology
• Term: from 2008 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 71800390

• Final Report Year: 2010

Final Report Abstract

We have identified alveolar sac associated proteins of alveolates and characterised a novel protein family, namely Alveolins. These proteins are encoded by gene families ranging from two genes in the ciliate Tetrahymena thermophila to more than a dozen as found in the apicomplexan parasite Toxoplasma gondii. They are highly soluble and predicted to form coil-coiled domains. In Plasmodium falciparum we were able to show they interact with proteins embedded in the alveolar membrane. We are the first to provide the molecular nexus uniting this super group. Proteomic profiling of the isolated pellicle from Tetrahymena thermophila has not only given us an insight into the proteomic content of this complex structure, but furthermore led to the identification of a remarkable feature found in many known and so far unknown proteins of the alveolate pellicle. More than a third of the proteins predicted to localise to the pellicle were found to contain charged repetitive motifs. These motifs vary in length, amount and distribution, and are present in many major proteins of the cytoskeleton/ pellicle of the ciliate T. thermophila. We have managed to localise several ,hypothetical proteinsʻ we identified in our screen and could show they belong to different cell-structures, but are always associated with the pellicle. We have started to search for homologs in other Alveolata with focus on apicomplexan parasites and identified many intriguing and potentially new protein-families. The localisation of one of the homolog proteins in T. gondii has led to the identification of the first conoid-ring protein and is consistent with our working hypothesis that Alveolata share many pellicle proteins and that charged repeat motifs are involved in the design of many of these structural proteins.

Publications

• (2008). A malaria parasite formin regulates actin polymerization and localizes to the parasiteerythrocyte moving junction during invasion. Cell Host and Microbe 13:188-198
  Baum J, Tonkin CJ, Paul AS, Rug M, Smith BJ, Gould SB, Richard D, Pollard TD, Cowman AF
  
• (2008). Alveolins, a new family of cortical proteins that define the protist infrakingdom Alveolata. Molecular Biology and Evolution 25:1219-30
  Gould SB, Tham WH, Cowman AF, McFadden GI, Waller RF
  
• (2008). Ariadneʻs thread: Guiding a precursor protein across five membranes in a cryptophyte. Journal of Phycology 44: 23-26
  Gould SB
  
• (2008). Plastid evolution. Annual Review of Plant Biology. 59:491-517
  Gould SB, McFadden GI, Waller RF
  
• (2009). A novel family of apicomplexan glideosome associated proteins With an innermembrane anchoring role. Journal of Biological Chemistry 284:25353
  Bullen HE, Tonkin CJ, O'Donnell RA, Tham WH, Papenfuss AT, Gould SB, Cowman AF, Crabb BS, Gilson PR