March 27, 2018
Josh Beck to be featured speaker for March 28 Biochemistry and Molecular Biophysics Seminar
Josh Beck, assistant professor of biomedical sciences at Iowa State University, will present "Transcending a self-imposed barrier: PTEX function in transport across the malaria parasite vacuole membrane" at 4 p.m. Wednesday, March 28, in 120 Ackert Hall, as part of the Biochemistry and Molecular Biophysics Seminar series.
Presentation abstract: Intraerythrocytic malaria parasites reside within a parasitophorous vacuolar membrane, or PVM, generated during host cell invasion. Erythrocyte remodeling and nutrient acquisition requires export of effector proteins and import of small molecules across this barrier between the parasite surface and host cell cytosol. The Plasmodium translocon of exported proteins, or PTEX, is crucial for protein export across the PVM, however the molecular basis of an observed PVM nutrient channel remains unknown. PTEX consists of three core proteins including the AAA+ ATPase chaperone HSP101 and two novel proteins known as PTEX150 and EXP2, hypothesized to serve a structural role and to form a membrane-spanning channel, respectively. While the critical importance of HSP101 and PTEX150 to protein export has been demonstrated, the contribution of EXP2 to parasite biology has remained obscure. Interrogating EXP2 function in Plasmodium falciparum by conditional knockdown revealed a critical role in protein export and blood-stage parasite survival. The expression timing and protein levels of HSP101 and PTEX150 are closely mirrored, peaking early in the ring stage. In contrast, EXP2 expression peaks in trophozoites, corresponding to an increased ratio of EXP2 to other PTEX components in the later part of the developmental cycle and implying a stoichiometry mismatch that suggests EXP2 may serve multiple roles in PVM biology. Accordingly, cell-attached patch clamp recordings on the PVM of extruded parasites revealed that the presence of the PVM nutrient channel is also dependent upon EXP2 expression levels and that mutations in EXP2 alter the voltage gating properties of the channel. Importantly, inactivation of HSP101 blocks protein export but does not impact this channel. Collectively, our results suggest that EXP2 serves dual roles as a protein-conducting pore in the context of PTEX and as a channel to facilitate small molecule passage across the PVM independent of HSP101. Our data may indicate a seemingly unprecedented dual functionality for a pore operating in its endogenous context.