Vesicle adaptors in malaria parasites show conservation and flexibility of protein sorting machinery.

Vesicle adaptors are critical for transport of proteins to the correct cellular destination. In malaria parasites general and specialized organelles depend on faithful protein transport to mediate host cell invasion and for intracellular survival. However, the role of adaptors in the parasite and the comparability of the sorting machinery with model organisms are unclear. Here, we show that AP-1, AP-3, and AP-4 are all important for parasite survival. AP-1 was needed for intracellular growth, biogenesis of specialized invasion organelles, and formation of invasive progeny, while AP-3 and AP-4 were both required for invasion into host cells. AP-1 acted through the multi-ligand receptor sortilin while AP-4 sorted multi-transmembrane proteins. Proxiomes from live cells revealed remarkable similarities of the configuration of the adaptor sorting machinery between the parasite and evolutionarily distant model organisms, but also unconventional features such as tepsin functioning with AP-1 and clathrin with AP-4. This work reveals unexpected exchangeability of key elements in otherwise surprisingly conserved adaptor sorting pathways.