Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and microneme proteins and in parasite division.

PLoS Pathog 2017 Apr 21;13(4):e1006331. Epub 2017 Apr 21.

Centre d'Infection et d'Immunité de Lille, Université de Lille, Inserm U1019, CNRS UMR 8204, CHU Lille, Institut Pasteur de Lille, Lille, France.

Toxoplasma gondii possesses a highly polarized secretory system, which efficiently assembles de novo micronemes and rhoptries during parasite replication. These apical secretory organelles release their contents into host cells promoting parasite invasion and survival. Using a CreLox-based inducible knock-out strategy and the ddFKBP over-expression system, we unraveled novel functions of the clathrin adaptor complex TgAP1. First, our data indicate that AP1 in T. gondii likely functions as a conserved heterotetrameric complex composed of the four subunits γ, β, μ1, σ1 and interacts with known regulators of clathrin-mediated vesicular budding such as the unique ENTH-domain containing protein, which we named Epsin-like protein (TgEpsL). Disruption of the μ1 subunit resulted in the mis-sorting of microneme proteins at the level of the Trans-Golgi-Network (TGN). Furthermore, we demonstrated that TgAP1 regulates rhoptry biogenesis by activating rhoptry protein exit from the TGN, but also participates in the post-Golgi maturation process of preROP compartments into apically anchored club-shaped mature organelles. For this latter activity, our data indicate a specific functional relationship between TgAP1 and the Rab5A-positive endosome-like compartment. In addition, we unraveled an original role for TgAP1 in the regulation of parasite division. APμ1-depleted parasites undergo normal daughter cell budding and basal complex assembly but fail to segregate at the end of cytokinesis.

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1006331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415223PMC
April 2017
5 Reads

Publication Analysis

Top Keywords

toxoplasma gondii
8
microneme proteins
8
clathrin adaptor
8
data indicate
8
parasite division
8
mis-sorting microneme
4
disruption μ1
4
μ1 subunit
4
subunit mis-sorting
4
protein tgepsl
4
named epsin-like
4
epsin-like protein
4
proteins level
4
tgepsl disruption
4
trans-golgi-network tgn
4
rhoptry biogenesis
4
biogenesis activating
4
activating rhoptry
4
rhoptry protein
4
regulates rhoptry
4

References

(Supplied by CrossRef)
A review on human toxoplasmosis
G Saadatnia et al.
Scand J Infect Dis 2012
Intravacuolar Membranes Regulate CD8
J Lopez et al.
T Cell Recognition of Membrane-Bound Toxoplasma gondii Protective Antigen. Cell Rep 2015
Golgi biogenesis in Toxoplasma gondii
L Pelletier et al.
Nature 2002

Similar Publications