Targeting of tail-anchored membrane proteins to subcellular organelles in Toxoplasma gondii

Traffic. 2016 Dec 19. doi: 10.1111/tra.12464. [Epub ahead of print]

Padgett LR¹, Arrizabalaga G^1,2, Sullivan WJ Jr^1,2.

Proper protein localization is essential for critical cellular processes, including vesicle-mediated transport and protein translocation. Tail-anchored (TA) proteins are integrated into organellar membranes via the C-terminus, orienting the N-terminus towards the cytosol. Localization of TA proteins occurs post-translationally and is governed by the C-terminus, which contains the integral transmembrane domain (TMD) and targeting sequence. Targeting of TA proteins is dependent on the hydrophobicity of the TMD as well as the length and composition of flanking amino acid sequences. We previously identified an unusual homologue of elongator protein, Elp3, in the apicomplexan parasite Toxoplasma gondii as a TA protein targeting the outer mitochondrial membrane. We sought to gain further insight into TA proteins and their targeting mechanisms using this early-branching eukaryote as a model. Our bioinformatics analysis uncovered 59 predicted TA proteins in Toxoplasma, nine of which were selected for follow-up analyses based on representative features. We identified novel TA proteins that traffic to specific organelles in Toxoplasma, including the parasite endoplasmic reticulum, mitochondrion, and Golgi apparatus. Domain swap experiments elucidated that targeting of TA proteins to these specific organelles was strongly influenced by the TMD sequence, including charge of the flanking C-terminal sequence.

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KEYWORDS:

Golgi apparatus; endoplasmic reticulum; membrane protein; mitochondria; protein localization; protein trafficking

PMID:

27991712

DOI:

10.1111/tra.12464