Ayong Lawrence, Raghavan Avanthi, Schneider Timothy G, Taraschi Theodore F, Fidock David A, Chakrabarti Debopam
Department of Molecular Biology and Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32826-3227, USA.
Eukaryot Cell. 2009 Sep;8(9):1330-40. doi: 10.1128/EC.00092-09. Epub 2009 Jul 17.
The specificity of vesicle-mediated transport is largely regulated by the membrane-specific distribution of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins. However, the signals and machineries involved in SNARE protein targeting to the respective intracellular locations are not fully understood. We have identified a Sec22 ortholog in Plasmodium falciparum (PfSec22) that contains an atypical insertion of the Plasmodium export element within the N-terminal longin domain. This Sec22 protein partially associates with membrane structures in the parasitized erythrocytes when expressed under the control of the endogenous promoter element. Our studies indicate that the atypical longin domain contains signals that are required for both endoplasmic reticulum (ER)/Golgi apparatus recycling of PfSec22 and partial export beyond the ER/Golgi apparatus interface. ER exit of PfSec22 is regulated by motifs within the alpha3 segment of the longin domain, whereas the recycling and export signals require residues within the N-terminal hydrophobic segment. Our data suggest that the longin domain of PfSec22 exhibits major differences from the yeast and mammalian orthologs, perhaps indicative of a novel mechanism for Sec22 trafficking in malaria parasites.
囊泡介导的运输特异性在很大程度上受SNARE（可溶性N - 乙基马来酰亚胺敏感因子附着蛋白受体）蛋白的膜特异性分布调控。然而，参与SNARE蛋白靶向各自细胞内位置的信号和机制尚未完全明了。我们在恶性疟原虫中鉴定出一种Sec22直系同源物（PfSec22），其在N端的longin结构域内含有疟原虫输出元件的非典型插入。当在其内源性启动子元件的控制下表达时，这种Sec22蛋白部分地与被寄生红细胞中的膜结构相关联。我们的研究表明，非典型的longin结构域包含PfSec22在内质网（ER）/高尔基体循环以及ER/高尔基体界面之外的部分输出所必需的信号。PfSec22从ER的输出受longin结构域α3片段内的基序调控，而循环和输出信号则需要N端疏水片段内的残基。我们的数据表明，PfSec22的longin结构域与酵母和哺乳动物的直系同源物存在重大差异，这可能表明疟原虫中Sec22运输的一种新机制。
