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恶性疟原虫 NIMA 相关激酶 Pfnek-1：性别特异性和对红内无性周期必需性的评估。

Plasmodium falciparum NIMA-related kinase Pfnek-1: sex specificity and assessment of essentiality for the erythrocytic asexual cycle.

机构信息

INSERM U609, Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8TA, UK.

INSERM-EPFL Joint Laboratory, Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, GHI-SV-EPFL Station 19, CH-1015 Lausanne, Switzerland.

出版信息

Microbiology (Reading). 2011 Oct;157(Pt 10):2785-2794. doi: 10.1099/mic.0.049023-0. Epub 2011 Jul 14.

DOI:10.1099/mic.0.049023-0
PMID:21757488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3353393/
Abstract

The Plasmodium falciparum kinome includes a family of four protein kinases (Pfnek-1 to -4) related to the NIMA (never-in-mitosis) family, members of which play important roles in mitosis and meiosis in eukaryotic cells. Only one of these, Pfnek-1, which we previously characterized at the biochemical level, is expressed in asexual parasites. The other three (Pfnek-2, -3 and -4) are expressed predominantly in gametocytes, and a role for nek-2 and nek-4 in meiosis has been documented. Here we show by reverse genetics that Pfnek-1 is required for completion of the asexual cycle in red blood cells and that its expression in gametocytes in detectable by immunofluorescence in male (but not in female) gametocytes, in contrast with Pfnek-2 and Pfnek-4. This indicates that the function of Pfnek-1 is non-redundant with those of the other members of the Pfnek family and identifies Pfnek-1 as a potential target for antimalarial chemotherapy. A medium-throughput screen of a small-molecule library provides proof of concept that recombinant Pfnek-1 can be used as a target in drug discovery.

摘要

疟原虫激酶组包括一个与 NIMA（不在有丝分裂中）家族相关的四个蛋白激酶（Pfnek-1 到 -4）家族，这些家族成员在真核细胞的有丝分裂和减数分裂中发挥重要作用。其中只有一个，Pfnek-1，我们之前在生化水平上进行了表征，在无性寄生虫中表达。其他三个（Pfnek-2、-3 和 -4）主要在配子体中表达，并且已经证明 nek-2 和 nek-4 在减数分裂中发挥作用。在这里，我们通过反向遗传学表明 Pfnek-1 是完成红细胞无性周期所必需的，并且其在配子体中的表达可以通过免疫荧光在雄性（但不是在雌性）配子体中检测到，与 Pfnek-2 和 Pfnek-4 形成对比。这表明 Pfnek-1 的功能与 Pfnek 家族的其他成员不同，并且鉴定 Pfnek-1 为抗疟化疗的潜在靶标。小分子文库的高通量筛选提供了概念验证，即重组 Pfnek-1 可以用作药物发现的靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c572/3353393/07ba5addc3f3/049023-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c572/3353393/82b8a0272140/049023-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c572/3353393/02dedd98554f/049023-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c572/3353393/ad9b49479e7d/049023-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c572/3353393/07ba5addc3f3/049023-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c572/3353393/82b8a0272140/049023-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c572/3353393/02dedd98554f/049023-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c572/3353393/ad9b49479e7d/049023-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c572/3353393/07ba5addc3f3/049023-f4.jpg

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