An Sfi1-like centrin-interacting centriolar plaque protein affects nuclear microtubule homeostasis.

Autor: Wenz C; Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany., Simon CS; Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany., Romão TP; Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany., Stürmer VS; Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany., Machado M; Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.; Graduate Program in Areas of Basic and Applied Biology, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal., Klages N; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Klemmer A; Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany., Voß Y; Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany., Ganter M; Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany., Brochet M; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Guizetti J; Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2023 May 02; Vol. 19 (5), pp. e1011325. Date of Electronic Publication: 2023 May 02 (Print Publication: 2023).
DOI: 10.1371/journal.ppat.1011325
Abstrakt: Malaria-causing parasites achieve rapid proliferation in human blood through multiple rounds of asynchronous nuclear division followed by daughter cell formation. Nuclear divisions critically depend on the centriolar plaque, which organizes intranuclear spindle microtubules. The centriolar plaque consists of an extranuclear compartment, which is connected via a nuclear pore-like structure to a chromatin-free intranuclear compartment. Composition and function of this non-canonical centrosome remain largely elusive. Centrins, which reside in the extranuclear part, are among the very few centrosomal proteins conserved in Plasmodium falciparum. Here we identify a novel centrin-interacting centriolar plaque protein. Conditional knock down of this Sfi1-like protein (PfSlp) caused a growth delay in blood stages, which correlated with a reduced number of daughter cells. Surprisingly, intranuclear tubulin abundance was significantly increased, which raises the hypothesis that the centriolar plaque might be implicated in regulating tubulin levels. Disruption of tubulin homeostasis caused excess microtubules and aberrant mitotic spindles. Time-lapse microscopy revealed that this prevented or delayed mitotic spindle extension but did not significantly interfere with DNA replication. Our study thereby identifies a novel extranuclear centriolar plaque factor and establishes a functional link to the intranuclear compartment of this divergent eukaryotic centrosome.
Competing Interests: The authors declare that they have no conflict of interest.
(Copyright: © 2023 Wenz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje