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Spatial relationships in pH signalling in a model filamentous fungus: roles of MVB pathway and plasma membrane components

丝状真菌模型 pH 信号传导的空间关系：MVB 途径和质膜成分的作用

基本信息

批准号：
BB/F01189X/1
负责人：
Herbert Arst
金额：
$ 49.49万
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF01189X%2F1
关键词：
Spatial relationships pH signalling model

项目摘要

A vitally important feature of the environment of an organism is the degree of acidity or alkalinity, i.e. the pH. Fungi tailor the combinations of the enzymes they secrete, the nutrient transporters they synthesise and the products (such as toxins and antibiotics) they export to the pH of their environment. The ability of fungi to adapt to a range of environmental pH is crucial to their ability to infect both plants and animals (including humans) and to their ability to produce toxins such as aflatoxin and antibiotics such as penicillin and cephalosporin. Our work is directed towards determining how a signal is triggered by environmental alkalinity, ultimately leading to the processing of a DNA-binding protein such that it is able to 'turn on' fungal genes whose action is appropriate to alkaline environments and 'turn off' those appropriate to acidic environments. Previous work has shown that seven proteins are exclusively involved of which one is the DNA-binding protein and the other six are involved in transmitting the pH signal. These six signalling proteins include two located at the cell surface, one of which facilitates localisation of the other which is probably the pH sensor, a protein interacting with one of the surface proteins, two proteins interacting with a component of the cellular protein-sorting machinery of which one also interacts with the DNA-binding protein and a protein-cutting enzyme involved in activating the DNA-binding protein. In addition, such signalling of environmental pH involves some components of intracellular structures whose other job is the sorting of certain proteins towards an appropriate location within the cell or towards destruction. In this project we will use the model filamentous fungus Aspergillus nidulans, a relatively benign organism but related to the serious opportunistic pathogen Aspergillus fumigatus, the aflatoxin-producing agricultural scourge Aspergillus flavus and the filamentous fungus used in the fermentation to produce sake Aspergillus oryzae. We shall determine which of the protein sorting components are involved in signalling environmental pH and examine the consequences of mutations affecting those components. In some cases these mutations seriously impair growth of the fungus but other mutations can abrogate that impairment. We shall determine the mechanism of abrogation. We shall determine whether the demands of pH signalling result in a shortage of those components also needed for protein sorting and whether the sorting machinery is able to attenuate pH signalling. Finally we will investigate how the localisation of the pH sensor at the cell surface is assisted by the other pH signalling cell surface protein.

一个生物体的环境的一个至关重要的特征是酸碱度，即pH值。真菌根据环境的pH值调整它们分泌的酶、它们合成的营养转运蛋白和它们输出的产物（如毒素和抗生素）的组合。真菌适应一系列环境pH值的能力对于它们感染植物和动物（包括人类）的能力以及产生黄曲霉毒素等毒素和青霉素和头孢菌素等抗生素的能力至关重要。我们的工作是针对确定信号是如何被环境碱度触发的，最终导致DNA结合蛋白的加工，使得它能够“打开”真菌基因，其作用适合碱性环境，并“关闭”那些适合酸性环境。先前的工作表明，七个蛋白质专门参与其中一个是DNA结合蛋白，其他六个参与传递pH信号。这六个信号蛋白包括两个位于细胞表面，其中一个促进定位的另一个可能是pH传感器，蛋白质与一个表面蛋白相互作用，两个蛋白质与细胞蛋白质分选机制的一个组成部分，其中一个也与DNA结合蛋白和蛋白质切割酶参与激活DNA结合蛋白相互作用。此外，这种环境pH的信号传导涉及细胞内结构的某些组分，其其他工作是将某些蛋白质分选到细胞内的适当位置或破坏。在本项目中，我们将使用模式丝状真菌构巢曲霉，一种相对良性的生物，但与严重的机会致病菌烟曲霉，产生黄曲霉毒素的农业鞭黄曲霉和用于发酵生产清酒的丝状真菌曲霉菌相关。我们将确定哪些蛋白质分选组分参与信号环境pH值，并检查影响这些组分的突变的后果。在某些情况下，这些突变严重损害真菌的生长，但其他突变可以消除这种损害。我们将确定废除的机制。我们将确定pH信号的需求是否会导致蛋白质分选所需的成分短缺，以及分选机械是否能够减弱pH信号。最后，我们将研究如何在细胞表面的pH传感器的本地化是由其他pH信号细胞表面蛋白的帮助。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Rescue of Aspergillus nidulans severely debilitating null mutations in ESCRT-0, I, II and III genes by inactivation of a salt-tolerance pathway allows examination of ESCRT gene roles in pH signalling.

DOI：
10.1242/jcs.088344
发表时间：
2011-12-01
期刊：
Journal of cell science
影响因子：
4
作者：
Calcagno-Pizarelli AM;Hervás-Aguilar A;Galindo A;Abenza JF;Peñalva MA;Arst HN Jr
通讯作者：
Arst HN Jr

Cytoplasmic dynein and early endosome transport.

DOI：
10.1007/s00018-015-1926-y
发表时间：
2015-09
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
0
作者：
Xiang X;Qiu R;Yao X;Arst HN Jr;Peñalva MA;Zhang J
通讯作者：
Zhang J

An ordered pathway for the assembly of fungal ESCRT-containing ambient pH signalling complexes at the plasma membrane.

DOI：
10.1242/jcs.098897
发表时间：
2012-04-01
期刊：
Journal of cell science
影响因子：
4
作者：
Galindo A;Calcagno-Pizarelli AM;Arst HN Jr;Peñalva MÁ
通讯作者：
Peñalva MÁ

Analysis of a novel calcium auxotrophy in Aspergillus nidulans.

DOI：
10.1016/j.fgb.2010.04.002
发表时间：
2010-07
期刊：
FUNGAL GENETICS AND BIOLOGY
影响因子：
3
作者：
Findon, Helen;Calcagno-Pizarelli, Ana-Maria;Martinez, Jose L.;Spielvogel, Anja;Markina-Inarrairaegui, Ane;Indrakumar, Tanya;Ramos, Jose;Penalva, Miguel A.;Espeso, Eduardo A.;Arst, Herbert N., Jr.
通讯作者：
Arst, Herbert N., Jr.

Characterization of Aspergillus nidulans DidB Did2, a non-essential component of the multivesicular body pathway.

DOI：
10.1016/j.fgb.2010.03.010
发表时间：
2010-07
期刊：
FUNGAL GENETICS AND BIOLOGY
影响因子：
3
作者：
Hervas-Aguilar, America;Rodriguez-Galan, Olga;Galindo, Antonio;Abenza, Juan F.;Arst, Herbert N., Jr.;Penalva, Miguel A.
通讯作者：
Penalva, Miguel A.