A Novel Family of Toxoplasma IMC Proteins Displays a Hierarchical Organization and Functions in Coordinating Parasite Division

PLoS Pathogens

Vern B. Carruthers¹  My-Hang Huynh¹  Imilce A. Rodriguez-Fernandez²  Peter J. Bradley²  Josh R. Beck²  Jessica Cruz de Leon³  Naomi S. Morrissette³ 

[1] Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America;Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America;Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California, United States of America

关键词: Cell membranes;    Membrane proteins;    Microtubules;    Parasitic diseases;    Toxoplasma;    Vacuoles;    Apicomplexa;    Cysteine;   

DOI  :  10.1371/journal.ppat.1001094

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Apicomplexans employ a peripheral membrane system called the inner membrane complex (IMC) for critical processes such as host cell invasion and daughter cell formation. We have identified a family of proteins that define novel sub-compartments of the Toxoplasma gondii IMC. These IMC Sub-compartment Proteins, ISP1, 2 and 3, are conserved throughout the Apicomplexa, but do not appear to be present outside the phylum. ISP1 localizes to the apical cap portion of the IMC, while ISP2 localizes to a central IMC region and ISP3 localizes to a central plus basal region of the complex. Targeting of all three ISPs is dependent upon N-terminal residues predicted for coordinated myristoylation and palmitoylation. Surprisingly, we show that disruption of ISP1 results in a dramatic relocalization of ISP2 and ISP3 to the apical cap. Although the N-terminal region of ISP1 is necessary and sufficient for apical cap targeting, exclusion of other family members requires the remaining C-terminal region of the protein. This gate-keeping function of ISP1 reveals an unprecedented mechanism of interactive and hierarchical targeting of proteins to establish these unique sub-compartments in the Toxoplasma IMC. Finally, we show that loss of ISP2 results in severe defects in daughter cell formation during endodyogeny, indicating a role for the ISP proteins in coordinating this unique process of Toxoplasma replication.

【 授权许可】

CC BY