Bio21 - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/369

Filters

2013 - 2014 2
2
Reset filters

Settings
Statistics
Citations
Author: BAUM, JACOB × Author: Hanssen, Eric × Author: RIGLAR, DAVID × End date: 2019 × Start date: 2010 ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    Membrane-Wrapping Contributions to Malaria Parasite Invasion of the Human Erythrocyte
    Dasgupta, S ; Auth, T ; Gov, NS ; Satchwell, TJ ; Hanssen, E ; Zuccala, ES ; Riglar, DT ; Toye, AM ; Betz, T ; Baum, J ; Gompper, G (CELL PRESS, 2014-07-01)
    The blood stage malaria parasite, the merozoite, has a small window of opportunity during which it must successfully target and invade a human erythrocyte. The process of invasion is nonetheless remarkably rapid. To date, mechanistic models of invasion have focused predominantly on the parasite actomyosin motor contribution to the energetics of entry. Here, we have conducted a numerical analysis using dimensions for an archetypal merozoite to predict the respective contributions of the host-parasite interactions to invasion, in particular the role of membrane wrapping. Our theoretical modeling demonstrates that erythrocyte membrane wrapping alone, as a function of merozoite adhesive and shape properties, is sufficient to entirely account for the first key step of the invasion process, that of merozoite reorientation to its apex and tight adhesive linkage between the two cells. Next, parasite-induced reorganization of the erythrocyte cytoskeleton and release of parasite-derived membrane can also account for a considerable energetic portion of actual invasion itself, through membrane wrapping. Thus, contrary to the prevailing dogma, wrapping by the erythrocyte combined with parasite-derived membrane release can markedly reduce the expected contributions of the merozoite actomyosin motor to invasion. We therefore propose that invasion is a balance between parasite and host cell contributions, evolved toward maximal efficient use of biophysical forces between the two cells.
  • Item
    Thumbnail Image
    Spatial association with PTEX complexes defines regions for effector export into Plasmodium falciparum-infected erythrocytes
    Riglar, DT ; Rogers, KL ; Hanssen, E ; Turnbull, L ; Bullen, HE ; Charnaud, SC ; Przyborski, J ; Gilson, PR ; Whitchurch, CB ; Crabb, BS ; Baum, J ; Cowman, AF (NATURE PUBLISHING GROUP, 2013-01)
    Export of proteins into the infected erythrocyte is critical for malaria parasite survival. The majority of effector proteins are thought to export via a proteinaceous translocon, resident in the parasitophorous vacuole membrane surrounding the parasite. Identification of the Plasmodium translocon of exported proteins and its biochemical association with exported proteins suggests it performs this role. Direct evidence for this, however, is lacking. Here using viable purified Plasmodium falciparum merozoites and three-dimensional structured illumination microscopy, we investigate remodelling events immediately following parasite invasion. We show that multiple complexes of the Plasmodium translocon of exported proteins localize together in foci that dynamically change in clustering behaviour. Furthermore, we provide conclusive evidence of spatial association between exported proteins and exported protein 2, a core component of the Plasmodium translocon of exported proteins, during native conditions and upon generation of translocation intermediates. These data provide the most direct cellular evidence to date that protein export occurs at regions of the parasitophorous vacuole membrane housing the Plasmodium translocon of exported proteins complex.