Integrins in disguise - mechanosensors in Saccharomyces cerevisiae as functional integrin analogues

Abstract

The ability to sense external mechanical stimuli is vital for all organisms. Integrins are transmembrane receptors that mediate bidirectional signalling between the extracellular matrix (ECM) and the cytoskeleton in animals. Thus, integrins can sense changes in ECM mechanics and can translate these into internal biochemical responses through different signalling pathways. In the model yeast species Saccharomyces cerevisiae there are no proteins with sequence similarity to mammalian integrins. However, we here emphasise that the WSC-type (Wsc1, Wsc2, and Wsc3) and the MID-type (Mid2 and Mtl1) mechanosensors in yeast act as partial functional integrin analogues. Various environmental cues recognised by these mechanosensors are transmitted by a conserved signal transduction cascade commonly referred to as the PKC1-SLT1 cell wall integrity (CWI) pathway. We exemplify the WSC- and MID-type mechanosensors functional analogy to integrins with a number of studies where they resemble the integrins in terms of both mechanistic and molecular features as well as in the overall phenotypic consequences of their activity. In addition, many important components in integrin-dependent signalling in humans are conserved in yeast; for example, Sla1 and Sla2 are homologous to different parts of human talin, and we propose that they together might be functionally similar to talin. We also propose that the yeast cell wall is a prominent cellular feature involved in sensing a number of external factors and subsequently activating different signalling pathways. In a hypothetical model, we propose that nutrient limitations modulate cell wall elasticity, which is sensed by the mechanosensors and results in filamentous growth. We believe that mechanosensing is a somewhat neglected aspect of yeast biology, and we argue that the physiological and molecular consequences of signal transduction initiated at the cell wall deserve more attention.