Cellular polarization is essential in morphogenesis, cell movement, and cell division. External or internal spatial cues determine the selection of the specific site where the growth machinery will be activated, and polarized growth will occur. This activation requires a perfect coordination among major cellular processes such as: cytoskeletal organization, secretion, and endocytosis. All this processes need to be controlled by the cell integrity pathway, and regulated by the cell cycle. Some of the major players involved in the establishment of polarized growth, such as Rho GTPases, PKCs and MAPK cascades are conserved from yeast to mammals suggesting that the basic mechanisms involved may have been conserved throughout evolution.

Our lab uses as model the fission yeast, Schizosaccharomyces pombe, which grows in a polarized manner at the cell ends generating rod-shaped cell of near-constant width. The morphology of the fission yeast, as that of other fungi, is restricted by the cell wall, a rigid structure that provides mechanical protection and supports the internal osmotic pressure of the cell. This structure is particularly important to maintain cell integrity during cytokinesis that requires coordinated closure of a contractile actomyosin ring and synthesis of a special wall named division septum.

Rho GTPases are essential in the establishment and regulation of growth, cytokinesis, and biosynthesis of the fission yeast cell wall. Our current aim is to study new Rho signaling pathways that were identified through a functional genomic approach by large-scale mapping of synthetic lethal interactions with mutants in genes coding Rho proteins and their regulators. The integrative approach undertaken will allow us to get an overall picture of the signaling inputs, molecular circuitry, and output responses mediated by Rho GTPases to maintain fission yeast polarized growth and cell integrity. In particular, we are focus on the functions of Rho1 and calcineurin which are antagonized by the MAPK signaling pathway particularly during the coordination of actomyosin ring contraction and cell wall biosynthesis in cytokinesis.

As a long term goal, we will investigate signaling pathways involved in the control of fungal cell integrity and growth that could be potentially used in the development of new antifungal drugs.

Figure 1. Scheme of the cell integrity signaling pathways in S. pombe. Rho1 and Rho2 regulate the synthesis of the fungal wall.These GTPases are regulated by GEFs like Rgf1 and GAPs like Rga2; Rga4, Rga6 and Rga7) and activate the targets (Glucan synthases and PKCs (Pck1 and Pck2). PKCs activate the MAPK signaling pathway that in turn antagonizes the function of Rho1 and Calcineurin.