A novel SUN1-ALLAN complex coordinates segregation of the bipartite MTOC across the nuclear envelope during rapid closed mitosis in Plasmodium DOI Open Access
Mohammad Zeeshan, Igor Blatov, Ryuji Yanase

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 5, 2024

Mitosis in eukaryotes involves reorganization of the nuclear envelope (NE) and microtubule-organizing centres (MTOCs). During male gametogenesis Plasmodium, causative agent malaria, mitosis is exceptionally rapid highly divergent. Within 8 min, haploid gametocyte genome undergoes three replication cycles (1N to 8N), while maintaining an intact NE. Axonemes assemble cytoplasm connect a bipartite MTOC-containing pole (NP) cytoplasmic basal body, producing eight flagellated gametes. The mechanisms coordinating NE remodelling, MTOC dynamics, flagellum assembly remain poorly understood. We identify SUN1-ALLAN complex as novel mediator remodelling coordination during Plasmodium gametogenesis. SUN1, conserved protein, localizes dynamic loops focal points at nucleoplasmic face spindle poles. ALLAN, divergent allantoicase, has location like that these proteins form unique complex, detected by live-cell imaging, ultrastructural expansion microscopy, interactomics. Deletion either SUN1 or ALLAN genes disrupts organization, leading body mis-segregation, defective assembly, impaired microtubule-kinetochore attachment, but axoneme formation remains intact. Ultrastructural analysis revealed miscoordination, aberrant gametes lacking material. These defects block development mosquito parasite transmission, highlighting essential functions this complex.

Язык: Английский

A scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei DOI Creative Commons
Thorey K. Jonsdottir, Martina Soledad Paoletta, Takahiro Ishizaki

и другие.

Nucleic Acids Research, Год журнала: 2025, Номер 53(2)

Опубликована: Янв. 11, 2025

Abstract Many Plasmodium genes remain uncharacterized due to low genetic tractability. Previous large-scale knockout screens have only been able target about half of the genome in more genetically tractable rodent malaria parasite berghei. To overcome this limitation, we developed a scalable CRISPR system called P. berghei high-throughput (PbHiT), which uses single cloning step generate targeting vectors with 100-bp homology arms physically linked guide RNA (gRNA) that effectively integrate into locus. We show PbHiT coupled gRNA sequencing robustly recapitulates known mutant phenotypes pooled transfections. Furthermore, provide an online resource and tagging designs entire scale-up vector production using ligation approach. This work presents for first time tool studying parasite’s biology at scale.

Язык: Английский

Процитировано

2
Genome-scale, functional screen of Plasmodium sexual replication DOI
Surendra K. Prajapati, Kim C. Williamson

Trends in Parasitology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Not just monkey business DOI Open Access
Robert W. Moon, Ellen Bushell

Science, Год журнала: 2025, Номер 387(6734), С. 582 - 583

Опубликована: Фев. 6, 2025

Functional genomics in malaria unlocks comparative biology across the family tree.

Язык: Английский

Процитировано

0
A comprehensive Schizosaccharomyces pombe atlas of physical transcription factor interactions with proteins and chromatin DOI Creative Commons

Merle Skribbe,

Charlotte Soneson, Michael Stadler

и другие.

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Transcription factors (TFs) are key regulators of gene expression, yet many their targets and modes action remain unknown. In Schizosaccharomyces pombe, one-third TFs solely homology predicted, with few experimentally validated. We created a comprehensive library 89 endogenously tagged S. pombe TFs, mapping protein chromatin interactions using immunoprecipitation-mass spectrometry immunoprecipitation sequencing. Our study identified interactors for half the over quarter potentially forming stable complexes. discovered DNA-binding sites most across 2,027 unique genomic regions, revealing motifs 38 uncovering complex network extensive TF cross- autoregulation. Characterization largest family revealed conserved DNA sequence preferences but diverse binding patterns repressive heterodimer, Ntu1/Ntu2, linked to perinuclear localization. TFexplorer webtool makes all data interactively accessible, offering insights into regulatory mechanisms broad biological relevance.

Язык: Английский

Процитировано

0
SUN-domain proteins of the malaria parasite Plasmodium falciparum are essential for proper nuclear division and DNA repair DOI Creative Commons

Sofiya Kandelis-Shalev,

Manish Goyal,

Tal Elam

и другие.

mBio, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

The protozoan parasite Plasmodium falciparum, which is responsible for the deadliest form of human malaria, accounts over half a million deaths year. These parasites proliferate in red blood cells by consecutive rounds closed mitoses called schizogony. Their virulence attributed to their ability modify infected adhere vascular endothelium and evade immunity through antigenic switches. Spatial dynamics at nuclear periphery were associated with regulation processes that enable establish long-term infection. However, our knowledge components envelope (NE) remains limited. One major protein complexes NE linker nucleoskeleton cytoskeleton (LINC) complex forms connecting bridge between cytoplasm nucleus interaction SUN KASH domain proteins. Here, we have identified two SUN-domain proteins as possible LINC P. falciparum show proper expression essential parasite's proliferation cells, depletion leads formation membranous whorls morphological changes NE. In addition, differential highlights different functions PfSUN2 specifically heterochromatin, while PfSUN1 activation DNA damage response. Our data provide indications involvement crucial biological intraerythrocytic development cycle malaria parasites. causing able thrive its host tight cellular processes, orchestrating cytoplasmic machineries are separated envelope. connect eukaryotes complex. was implicated several important functions, role biology unknown. identify demonstrate they parasites' blood, cell. activating response association heterochromatin. evidence roles cell cycle.

Язык: Английский

Процитировано

0
A novel SUN1-ALLAN complex coordinates segregation of the bipartite MTOC across the nuclear envelope during rapid closed mitosis in Plasmodium DOI Open Access
Mohammad Zeeshan, Igor Blatov, Ryuji Yanase

и другие.

Опубликована: Апрель 10, 2025

Mitosis in eukaryotes involves reorganization of the nuclear envelope (NE) and microtubule-organizing centres (MTOCs). During male gametogenesis Plasmodium, causative agent malaria, mitosis is exceptionally rapid highly divergent. Within 8 min, haploid gametocyte genome undergoes three replication cycles (1N to 8N), while maintaining an intact NE. Axonemes assemble cytoplasm connect a bipartite MTOC-containing pole (NP) cytoplasmic basal body, producing eight flagellated gametes. The mechanisms coordinating NE remodelling, MTOC dynamics, flagellum assembly remain poorly understood.We identify SUN1-ALLAN complex as novel mediator remodelling coordination during Plasmodium gametogenesis. SUN1, conserved protein, localizes dynamic loops focal points at nucleoplasmic face spindle poles. ALLAN, divergent allantoicase, has location like that these proteins form unique complex, detected by live-cell imaging, ultrastructural expansion microscopy, interactomics. Deletion either SUN1 or ALLAN genes disrupts organization, leading body mis-segregation, defective assembly, impaired microtubule-kinetochore attachment, but axoneme formation remains intact. Ultrastructural analysis revealed miscoordination, aberrant gametes lacking material. These defects block development mosquito parasite transmission, highlighting essential functions this complex.

Язык: Английский

Процитировано

0
A novel SUN1-ALLAN complex coordinates segregation of the bipartite MTOC across the nuclear envelope during rapid closed mitosis in Plasmodium DOI Open Access
Mohammad Zeeshan, Igor Blatov, Ryuji Yanase

и другие.

Опубликована: Апрель 10, 2025

Mitosis in eukaryotes involves reorganization of the nuclear envelope (NE) and microtubule-organizing centres (MTOCs). During male gametogenesis Plasmodium, causative agent malaria, mitosis is exceptionally rapid highly divergent. Within 8 min, haploid gametocyte genome undergoes three replication cycles (1N to 8N), while maintaining an intact NE. Axonemes assemble cytoplasm connect a bipartite MTOC-containing pole (NP) cytoplasmic basal body, producing eight flagellated gametes. The mechanisms coordinating NE remodelling, MTOC dynamics, flagellum assembly remain poorly understood.We identify SUN1-ALLAN complex as novel mediator remodelling coordination during Plasmodium gametogenesis. SUN1, conserved protein, localizes dynamic loops focal points at nucleoplasmic face spindle poles. ALLAN, divergent allantoicase, has location like that these proteins form unique complex, detected by live-cell imaging, ultrastructural expansion microscopy, interactomics. Deletion either SUN1 or ALLAN genes disrupts organization, leading body mis-segregation, defective assembly, impaired microtubule-kinetochore attachment, but axoneme formation remains intact. Ultrastructural analysis revealed miscoordination, aberrant gametes lacking material. These defects block development mosquito parasite transmission, highlighting essential functions this complex.

Язык: Английский

Процитировано

0
A CRISPR homing screen finds a chloroquine resistance transporter-like protein of the Plasmodium oocyst essential for mosquito transmission of malaria DOI Creative Commons

Arjun Balakrishnan,

Mirjam Hunziker, Puja Tiwary

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 24, 2025

Язык: Английский

Процитировано

0
A novel SUN1-ALLAN complex coordinates segregation of the bipartite MTOC across the nuclear envelope during rapid closed mitosis in Plasmodium DOI Open Access
Mohammad Zeeshan, Igor Blatov, Ryuji Yanase

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 5, 2024

Mitosis in eukaryotes involves reorganization of the nuclear envelope (NE) and microtubule-organizing centres (MTOCs). During male gametogenesis Plasmodium, causative agent malaria, mitosis is exceptionally rapid highly divergent. Within 8 min, haploid gametocyte genome undergoes three replication cycles (1N to 8N), while maintaining an intact NE. Axonemes assemble cytoplasm connect a bipartite MTOC-containing pole (NP) cytoplasmic basal body, producing eight flagellated gametes. The mechanisms coordinating NE remodelling, MTOC dynamics, flagellum assembly remain poorly understood. We identify SUN1-ALLAN complex as novel mediator remodelling coordination during Plasmodium gametogenesis. SUN1, conserved protein, localizes dynamic loops focal points at nucleoplasmic face spindle poles. ALLAN, divergent allantoicase, has location like that these proteins form unique complex, detected by live-cell imaging, ultrastructural expansion microscopy, interactomics. Deletion either SUN1 or ALLAN genes disrupts organization, leading body mis-segregation, defective assembly, impaired microtubule-kinetochore attachment, but axoneme formation remains intact. Ultrastructural analysis revealed miscoordination, aberrant gametes lacking material. These defects block development mosquito parasite transmission, highlighting essential functions this complex.

Язык: Английский

Процитировано

2