Morand Sabine, Renggli Christina Kunz, Roditi Isabel, Vassella Erik
Institut für Zellbiologie, Universität Bern, Switzerland.
Mol Biochem Parasitol. 2012 Nov;186(1):73-6. doi: 10.1016/j.molbiopara.2012.09.001. Epub 2012 Sep 8.
MAP kinase kinase 1 (MKK1) is encoded by a single copy gene in Trypanosoma brucei. It has been shown recently that MKK1 is not essential for bloodstream forms [14]. To investigate the requirement for MKK1 in other life-cycle stages we generated null mutants in procyclic forms of a fly-transmissible strain. These grew normally in culture and were able to establish midgut infections in tsetse at normal rates and intensities, but were incapable of colonising the salivary glands. Transformation of null mutants with an ectopic copy of MKK1 enabled parasites to complete the life cycle in tsetse and infect mice. This is the first example of a gene that is indispensable for transmission of T. brucei. It also raises the possibility that activating the MKK1 signalling cascade in vitro might trigger the differentiation and proliferation of life-cycle stages of T. brucei that are currently refractory to culture.
丝裂原活化蛋白激酶激酶1（MKK1）由布氏锥虫中的单拷贝基因编码。最近的研究表明，MKK1对于血流形式并非必需[14]。为了研究MKK1在其他生命周期阶段的需求，我们在一种可通过苍蝇传播的菌株的前循环形式中生成了无效突变体。这些突变体在培养中正常生长，能够以正常的速率和强度在采采蝇的中肠建立感染，但无法在唾液腺中定殖。用MKK1的异位拷贝转化无效突变体，使寄生虫能够在采采蝇中完成生命周期并感染小鼠。这是布氏锥虫传播所必需的基因的首个实例。这也增加了在体外激活MKK1信号级联可能触发目前难以培养的布氏锥虫生命周期阶段的分化和增殖的可能性。
