title: In depth functional characterization of Plasmodium berghei ferlin-like protein
creator: Obrova, Klara
subject: ddc-570
subject: 570 Life sciences
description: Proteins of the ferlin family mediate calcium-dependent vesicular fusion. Although present throughout eukaryotic evolution, their function in unicellular organisms including apicomplexan parasites is unknown.  This study defined for the first time a crucial role for a ferlin-like protein (FLP) in host-to-vector transmission of the rodent malaria parasite Plasmodium berghei. Analysis of flp expression profile revealed a peak in the gametocyte stage. Endogenous tagging of the protein confirmed high abundance of FLP in this stage. In agreement with the reported vesicular localization of ferlins, HA-tagged FLP labelled intracellular speckles in asexual and sexual blood stages. The FLP-labelled vesicles relocalized to the cell periphery during gamete maturation, suggesting that they might act in the process of the gamete egress from the red blood cell.  Infection of the mosquito vectors requires the formation of free gametes and their fertilization in the mosquito midgut. Mature gametes will only emerge upon secretion of factors that stimulate the disruption of the red blood cell membrane and the parasitophorous vacuole membrane. Lysis of the surrounding membranes is a critical step in host-to-vector transmission and its failure prevents infection of the mosquito.  Genetic depletion of FLP in sexual stages led to a complete life cycle arrest in the mosquito. Although mature gametes formed normally, mutants lacking FLP remained trapped in the red blood cell. FLP function was restricted to egress as the observed phenotype was rescued by detergent-mediated in vitro membrane lysis facilitating escape from the host cell and allowing normal life cycle progression of the FLP-depleted gametocytes. The data of this work define FLP as a novel critical factor for Plasmodium fertilization and transmission and suggest an evolutionarily conserved example of ferlin-mediated exocytosis.
date: 2018
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/25608/1/PhD%20thesis%20print.pdf
identifier: DOI:10.11588/heidok.00025608
identifier: urn:nbn:de:bsz:16-heidok-256087
identifier:   Obrova, Klara  (2018) In depth functional characterization of Plasmodium berghei ferlin-like protein.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/25608/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng