Project Details
Projekt
The role of the Gliding-Initiation-Complex during host cell egress of Toxoplasma gondii
Subject Area
Parasitology and Biology of Tropical Infectious Disease Pathogens
Term
from 2021 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 446108401
Apicomplexans such as Plasmodium spp. and Toxoplasma gondii are obligate intracellular parasites. During replication, daughter parasites are formed within a single mother and an intravacuolar network that connects parasites, allowing material transfer, organellar recycling and coordination of synchronised replication, is established. This intravacuolar network relies on F-actin polymerisation and rapidly breaks down prior to egress. Failure of network disassembly results in parasites being unable to egress from the host cell. During the last funding period we identified several novel factors that act at distinct steps during this process (Li et al., Nature Microbiology 2022 [1]). While the signalling linking factor (SLF) acts upstream of network disassembly, the conoid gliding protein (CGP) acts after the disassembly of the network to initiate gliding motility of the parasite. No information exists regarding the exact function of CGP which is localised to the apical tip (conoid) of the parasite. In preliminary experiments, we established that it interacts with the actin nucleator Formin-1 (FRM1) and a putative histone methyltransferase (PCKMT). Furthermore, we performed proximity labelling to identify additional, putative components associated with this complex, which we termed GIC (Gliding Initiation Complex). To close major gaps in our understanding of GIC, we will focus on two major objectives: 1. Identification and analysis of CGP interacting proteins that form the Gliding Initiation Complexes (GIC). 2. Analysis of the dynamic behaviour of gliding initiation proteins during EXIT and invasion This project fits to Exit Pathway 2: Active host cell destruction, including lysis of the vacuolar compartment and the plasma membrane as well as destruction of cysts.
DFG Programme
Priority Programmes
Subproject of
SPP 2225:
Exit strategies of intracellular pathogens
