TY - JOUR
T1 - Rounding precedes rupture and breakdown of vacuolar membranes minutes before malaria parasite egress from erythrocytes
AU - Glushakova, Svetlana
AU - Beck, Josh R.
AU - Garten, Matthias
AU - Busse, Brad L.
AU - Nasamu, Armiyaw S.
AU - Tenkova-Heuser, Tatyana
AU - Heuser, John
AU - Goldberg, Daniel E.
AU - Zimmerberg, Joshua
N1 - Publisher Copyright:
© 2018 John Wiley & Sons Ltd
PY - 2018/10
Y1 - 2018/10
N2 - Because Plasmodium falciparum replicates inside of a parasitophorous vacuole (PV) within a human erythrocyte, parasite egress requires the rupture of two limiting membranes. Parasite Ca2+, kinases, and proteases contribute to efficient egress; their coordination in space and time is not known. Here, the kinetics of parasite egress were linked to specific steps with specific compartment markers, using live-cell microscopy of parasites expressing PV-targeted fluorescent proteins, and specific egress inhibitors. Several minutes before egress, under control of parasite [Ca2+]i, the PV began rounding. Then after ~1.5 min, under control of PfPKG and SUB1, there was abrupt rupture of the PV membrane and release of vacuolar contents. Over the next ~6 min, there was progressive vacuolar membrane deterioration simultaneous with erythrocyte membrane distortion, lasting until the final minute of the egress programme when newly formed parasites mobilised and erythrocyte membranes permeabilised and then ruptured—a dramatic finale to the parasite cycle of replication.
AB - Because Plasmodium falciparum replicates inside of a parasitophorous vacuole (PV) within a human erythrocyte, parasite egress requires the rupture of two limiting membranes. Parasite Ca2+, kinases, and proteases contribute to efficient egress; their coordination in space and time is not known. Here, the kinetics of parasite egress were linked to specific steps with specific compartment markers, using live-cell microscopy of parasites expressing PV-targeted fluorescent proteins, and specific egress inhibitors. Several minutes before egress, under control of parasite [Ca2+]i, the PV began rounding. Then after ~1.5 min, under control of PfPKG and SUB1, there was abrupt rupture of the PV membrane and release of vacuolar contents. Over the next ~6 min, there was progressive vacuolar membrane deterioration simultaneous with erythrocyte membrane distortion, lasting until the final minute of the egress programme when newly formed parasites mobilised and erythrocyte membranes permeabilised and then ruptured—a dramatic finale to the parasite cycle of replication.
KW - Plasmodium falciparum
KW - infection
KW - membrane
KW - microbial structure
KW - microbial–cell interaction
KW - parasitophorous vacuole
UR - http://www.scopus.com/inward/record.url?scp=85050459784&partnerID=8YFLogxK
U2 - 10.1111/cmi.12868
DO - 10.1111/cmi.12868
M3 - Article
C2 - 29900649
AN - SCOPUS:85050459784
SN - 1462-5814
VL - 20
JO - Cellular microbiology
JF - Cellular microbiology
IS - 10
M1 - e12868
ER -