Introduction
Our work focuses on the role of the cytoskeleton in the pathogenic fungus Ustilago maydis. Being related to phytopathology, microbiology and molecular cell biology, our work serves two main objectives explained here.
Understanding the role of the cytoskeleton in fungal growth and pathogenicity
Fungi are often considered to be harmless mushrooms that enrich our diet. However, many fungi are human and plant pathogens that pose a serious threat to public health and agriculture. Among these are human pathogens such as Aspergillus fumingatus, which causes life-threatening invasive Aspergillosis in immunocompromised patients1 and Candida albicans, which is responsible for approximately 10,000 death per year in the USA2 Examples of plant pathogens include the rice blast Magnaporthe grisea and the corn smut fungus Ustilago maydis; both of which cause severe crop diseases (Figure 1) and are therefore even be considered as potential bioweapons3.
Whereas all these fungal pathogens differ in their host spectrum and their detailed mechanisms of infection, what they have in common is that they invade the host by forming a filamentous cell chain, the so-called fungal hypha. This tissue-invasive form expands at the growing tip, which is also the release site of lytic enzymes that soften the host tissue, thereby supporting entry of the pathogen. It emerges that hyphal growth relies on the fibres of the cytoskeleton. These fibres run throughout the hyphal cells and provide tracks for mechanoenzymes, so-called molecular motors, which 'walk' along the cytoskeleton and thereby deliver growth supplies to the growing hyphal tip4. Without this constant supply hyphal growth ceases and infection stops; this explains the crucial importance of the cytoskeleton in fungal pathogenicity. Furthermore, the cytoskeleton is essential during mitosis, a process that is of vital importance for all eukaryotes.
Considering the importance of the cytoskeleton for fungal virulence, it is not surprising that some of the most potent anti-fungal drugs are targeting the cytoskeleton. However, rapid development of fungicide resistance makes the search for new fungicides urgent and requires a more detailed understanding of the molecular basis of hyphal growth. Using U. maydis as a pathogenic model fungus, our work sets out to discover the structural basis and general mechanisms by which the cytoskeleton supports fungal pathogenicity.
Using U. maydis as a model to understand fundamental principles of molecular motor function
Communication and long-distance transport is a crucial requirement for organization and function of mammalian cells. Intracellular motility is mediated by molecular motors, and defects in motor function are implied in many neurological diseases5.
The genome of humans contains approximately 90 different motors. Although not all motors are expressed in each cell type, numerous motors operate simultaneously in living cells, such as neurons of the brain. This complex situation, together with technical disadvantages, makes it difficult to analyse motor function in such mammalian cells. However, motor-based transport is an early invention in evolution. Simple fungal organisms use similar core transport machineries (Figure 2) and can therefore serve as model systems to address fundamental questions concerning intracellular motility and the cytoskeleton.
Our work aims to determine fundamental principles of how molecular motors organize the cell and mediate long distance transport. As well as addressing the role of dynein in mitosis, we focus on the function and regulation of kinesin-1 (in humans: Kif5), kinesin-3 (in humans: Kif1A) and dynein in long-distance bi-directional transport of early endosomes. Because these motors are also central players in mammalian axonal transport, our work promises to provide insight into the mechanism of intracellular transport in neurons.
1 Brakhage & Langfelder (2002) Annu. Rev. Microbiol. 56:433-455.
2 Sudbery, Gow, Berman (2004) Trends Microbiol. 12:317-324.
3 Madden & Wheelis (2003) Annu. Rev. Phytopathol. 41:155-176.
4 Steinberg (2007) Eurkaryot. Cell, 6:351-360.
5 Chevalier-Larsen & Holzbaur (2006) Biochim Biophys Acta. 1762:1094-1108.
Figure 1: Symptoms of corn smut disease caused by Ustilago maydis (from Brefeld 1983, Untersuchungen aus dem Gesamtgebiet der Mykologie. 5, 67).
Figure 2: Comparison of the microtubule-based transport machinery in neurons and in Ustilago maydis. Note that neurons have many more kinesin motors being involved in microtubule organization and trafficking (image taken from Steinberg and Perez-Martin, 2008, Trends Cell Biol. 18:61).