Molecular mechanisms of mechanosensing and their roles in fungal contact sensing

Abstract

Numerous fungal species respond to contact with a surface by undergoing differentiation. Contact between plant pathogenic fungi and a surface results in the elaboration of the complex structures that enable invasion of the host plant, and for the opportunistic human pathogen Candida albicans, contact with a semi-solid surface results in invasive growth into the subjacent material. The ability to sense contact with an appropriate surface therefore contributes to the ability of these fungi to cause disease in their respective hosts. This Review discusses molecular mechanisms of mechanosensitivity, the proteins involved, such as mechanosensitive ion channels, G-protein-coupled receptors and integrins, and their putative roles in fungal contact sensing.

Figure 1. Candida albicans differentiation

a. Colonies growing on the surface of agar medium were washed off the medium and cells that had invaded the agar were examined. A cross section of the agar plate is shown (left image). The white arrowhead indicates the top of the agar and the black arrow indicates an invading filament. The central image shows cells that were inoculated into a rabbit ligated ileal loop. A section of the ileum stained with Gomori methenamine silver is shown; the lumen is above. The arrow indicates filamentous fungal cells (dark stain) invading the gut-associated lymphoid tissue. The right image shows a micrograph of a mature Candida albicans biofilm composed of yeast-form cells and filamentous cells. b. Several environmental cues — contact, nutrients, temperature and pH — promote the conversion of yeast-form cells to filamentous hyphae. Micrograph courtesy of L. Julia Douglas, Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, University of Glasgow.

Figure 2. Function of mechanosensitive ion channels

a. A structural model of Mycobacterium tuberculosis MscL in the closed state is shown on the left; the central and right images show the effect of the membrane environment on the conformation of MscL. In a symmetric environment, such as a liposome that is composed of dioleoyl-phosphatidylcholine (PC), MscL is in the closed conformation. When the cone-shaped, amphiphilic molecule lysophosphatidylcholine (LPC) is inserted into one leaflet of the bilayer, perturbation of the bilayer results in opening of the channel. b. Model of the role of mechanosensitive (MS) channels in Candida albicans thigmotropism. A growing germ tube contacting a ridge is illustrated. When the tip of the hypha contacts the ridge, membrane deformation occurs, resulting in MS channel opening. In other parts of the germ tube, MS channels are closed. The structural model in part a is reproduced, with permission, from Ref. © (2007) Macmillan publishers limited. All rights reserved. The rest of part a is adapted, with permission, from Ref. © (2002) Macmillan publishers limited. All rights reserved.

Figure 3. Sensing of cytoskeletal forces

a. Focal adhesion in an adherent mammalian cell is depicted. Integrins bind to the extracellular matrix (ECM) and anchor the cell. Integrins are part of focal adhesions, which are connected to stress fibres composed of actin and actin-associated proteins. Inward contractile force is exerted by molecular motors. b. In this model of a fungal cell, the cell wall and plasma membrane are held together by hypothetical transmembrane plasma-membrane proteins. An anchorage site — a large complex of transmembrane and cytoplasmic proteins — is bound by cytoskeletal elements. Turgor pressure provides an outward force and molecular motors pull inwards. The balance of forces is sensed and membrane perturbation caused by contact might alter the balance of forces.