External lipid PI3P mediates entry of eukaryotic pathogen effectors into plant and animal host cells.
Pathogens of plants and animals produce effector proteins that are transferred into the cytoplasm of host cells to suppress host defenses. One type of plant pathogens, oomycetes, produces effector proteins with N-terminal RXLR and dEER motifs that enable entry into host cells. We show here that effectors of another pathogen type, fungi, contain functional variants of the RXLR motif, and that the oomycete and fungal RXLR motifs enable binding to the phospholipid, phosphatidylinositol-3-phosphate (PI3P). We find that PI3P is abundant on the outer surface of plant cell plasma membranes and, furthermore, on some animal cells. All effectors could also enter human cells, suggesting that PI3P-mediated effector entry may be very widespread in plant, animal and human pathogenesis. Entry into both plant and animal cells involves lipid raft-mediated endocytosis. Blocking PI3P binding inhibited effector entry, suggesting new therapeutic avenues.
Kale
Shiv D
SD
Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Gu
Biao
B
Capelluto
Daniel G S
DG
Dou
Daolong
D
Feldman
Emily
E
Rumore
Amanda
A
Arredondo
Felipe D
FD
Hanlon
Regina
R
Fudal
Isabelle
I
Rouxel
Thierry
T
Lawrence
Christopher B
CB
Shan
Weixing
W
Tyler
Brett M
BM
D020418:Algal Proteins / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D008969:Molecular Sequence Data; D009868:Oomycetes / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010944:Plants / Q000382:microbiology
D020418:Algal Proteins; D005656:Fungal Proteins; D018129:Phosphatidylinositol Phosphates