Contents lists available at ScienceDirect Parasitology International journal homepage: www.elsevier.com/locate/parint G-strand binding protein 2 is involved in asexual and sexual development of Plasmodium berghei Mamoru Niikura a, ⁎ , Toshiyuki Fukutomi b , Kana Fukui a , Shin-Ichi Inoue c , Hiroko Asahi a , Fumie Kobayashi d a Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan b Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan c Division of Immunology, Department of Molecular Microbiology and Immunology, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan d Department of Environmental Science, School of Life and Environmental Science, Azabu University, Japan ARTICLE INFO Keywords: Apicomplexa Malaria GBP2 Comparative proteomics Gametocyte ABSTRACT G-strand binding protein 2 (GBP2) is a Ser/Arg-rich (SR) protein involved in mRNA surveillance and nuclear mRNA quality control in yeast. However, the roles of GBP2 in virulence and sexual development in Plasmodium parasites are unclear, although GBP2 is involved in the asexual development of Plasmodium berghei, the rodent malaria parasite. In this study, we investigated the role of GBP2 in virulence and sexual development of P. berghei using gbp2-deleted P. berghei (Δgbp2 parasites). Then, to identify factors affected by gbp2 deletion, we performed a comparative proteomic analysis of the Δgbp2 parasites. We found that GBP2 was not associated with the development of experimental cerebral malaria during infection with P. berghei, but asexual development of the parasite was delayed with deletion of gbp2. However, the development of P. berghei gametocytes was sig- nificantly reduced with deletion of gbp2. Comparative proteomic analysis revealed that the levels of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and hypoxanthine-guanine phosphoribosyl- transferase (HGPRT) in Δgbp2 parasites were significantly higher than those in wild-type (WT) parasites, sug- gesting that biosynthesis of purine nucleotides may be involved in function of GBP2. Therefore, we investigated the effect of purine starvation on the sexual development and proteome. In nt1-deleted P. berghei (Δnt1 para- sites), the production of male and female gametocytes was significantly reduced compared to that in WT parasites. Moreover, we found that protein levels of GBP2 in Δnt1 parasites were markedly lower than in WT parasites. These findings suggest that GBP2 is primarily involved in the sexual development of malaria parasites, and its function may be suppressed by purine starvation. 1. Introduction Malaria is a devastating parasitic disease of humans in tropical and subtropical regions. The asexual blood stages of the parasite are the cause of severe diseases, such as cerebral malaria and severe anemia. In 2017, an estimated 219 million people were diagnosed with malaria, of whom 435,000 died [1]. The control of gene expression is crucial for the virulence and asexual and sexual development of malaria parasites. ApiAP2 tran- scription factors control gene expression during the life-cycle of api- complexan parasites, such as Plasmodium species [2]. Post-transcrip- tional regulation of gene expression by RNA-binding proteins (RBPs) also plays important roles in parasite biology, in particular during the sexual development of malaria parasites [3]. DOZI (PF3D7_0320800), CITH (PF3D7_1474900), and PUF2 (PF3D7_0417100) regulate gene expression during sexual development of Plasmodium parasites [4,5]. The transcription-export (TREX) complex is a multi-subunit com- plex that acts as a suppressor of the transcriptional defect of Hpr1 caused by the overexpression (THO) subcomplex, U2AF65-associated protein (UAP56), and ALWAYS EARLY (ALY) [6]. In Opisthokonta, TREX complex is involved in the export of mRNA in a Ran-independent manner [7,8]. UAP56 (Sub2 complex in yeast) interacts with the THO subcomplex and is associated with recruitment of the mRNA export receptor, nuclear RNA export factor 1/NTF2-related export protein-1 (NXF1/NXT1) complex (Mex67/Mtr2 complex in yeast), through in- teraction with ALY (YRA1 in yeast) [9]. In yeast, recruitment of the Mex67/Mtr2 complex also involves various mRNA export adaptor proteins, nuclear poly (A) binding https://doi.org/10.1016/j.parint.2020.102059 Received 5 May 2019; Received in revised form 6 January 2020; Accepted 14 January 2020 ⁎ Corresponding author at: Department of Infectious Diseases, Kyorin University School of Medicine, 6–20–2 Shinkawa, Mitaka, Tokyo 181–8611, Japan. E-mail address: mniikura@ks.kyorin-u.ac.jp (M. Niikura). Parasitology International 76 (2020) 102059 Available online 18 January 2020 1383-5769/ © 2020 Elsevier B.V. All rights reserved. T