Myosin A tail domain interacting protein (MTIP) localizes to the inner membrane complex of Plasmodium sporozoites.
Apicomplexan host cell invasion and gliding motility depend on the parasite's actomyosin system located beneath the plasma membrane of invasive stages. Myosin A (MyoA), a class XIV unconventional myosin, is the motor protein. A model has been proposed to explain how the actomyosin motor operates but little is known about the components, topology and connectivity of the motor complex. Using the MyoA neck and tail domain as bait in a yeast two-hybrid screen we identified MTIP, a novel 24 kDa protein that interacts with MyoA. Deletion analysis shows that the 15 amino-acid C-terminal tail domain of MyoA, rather than the neck domain, specifically interacts with MTIP. In Plasmodium sporozoites MTIP localizes to the inner membrane complex (IMC), where it is found clustered with MyoA. The data support a model for apicomplexan motility and invasion in which the MyoA motor protein is associated via its tail domain with MTIP, immobilizing it at the outer IMC membrane. The head domain of the immobilized MyoA moves actin filaments that, directly or via a bridging protein, connect to the cytoplasmic domain of a transmembrane protein of the TRAP family. The actin/TRAP complex is then redistributed by the stationary MyoA from the anterior to the posterior end of the zoite, leading to its forward movement on a substrate or to penetration of a host cell.
Bergman
Lawrence W
LW
Division of Molecular Parasitology, Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA. lawrence.bergman@drexel.edu
Kaiser
Karine
K
Fujioka
Hisashi
H
Coppens
Isabelle
I
Daly
Thomas M
TM
Fox
Sarah
S
Matuschewski
Kai
K
Nussenzweig
Victor
V
Kappe
Stefan H I
SH
D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification*; D002451:Cell Compartmentation / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002465:Cell Movement / Q000235:genetics*; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D006790:Host-Parasite Interactions / Q000235:genetics; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification*; D008854:Microscopy, Electron; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000235:genetics / Q000302:isolation & purification*; D008969:Molecular Sequence Data; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D010967:Plasmodium yoelii / Q000378:metabolism* / Q000472:pathogenicity / Q000648:ultrastructure; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D034101:Sporozoites / Q000378:metabolism* / Q000472:pathogenicity / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; C477148:MTIP protein, Plasmodium yoelii; D046911:Macromolecular Substances; D008565:Membrane Proteins; D020409:Molecular Motor Proteins; D015800:Protozoan Proteins; C076139:sporozoite-surface protein 2, Plasmodium yoelli; D024507:Nonmuscle Myosin Type IIA