Pilar Pérez

Rho GTPases regulation of polarized growth

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 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. Cytokinesis is the final step of the cell cycle and occurs at the end of mitosis. 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. As in other walled organism, cytokinesis 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 function of Rho1 and its regulatory proteins in cell integrity and in the coordination of actomyosin ring contraction and cell wall biosynthesis during 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.

Rho1 positive regulators (GEFs: Rgf1, Rgf2 and Rgf3); negative regulators (GAPs Rga1; Rga5 and Rga8), and Targets (Glucan stnthases (Bgs); PKC (Pck1 and Pck2); other proteins (Pxl1); in Schizosaccharomyces pombe

Group members
José Márquez Technician
Rebeca Martín Postdoctoral
Pilar Pérez Research Professor (CSIC)
Pedro M. Coll Assistant Professor (USAL)
Victor Arriba PhD Student
Elvira Portales Technician
Recent publications
Pérez P, Cortés J.C., Martín-García R, Ribas J.C. (2016).
Overview of fission Yeast septation
Cell Microbiol. 18: 1201-1207.
Revilla-Guarinos M.T., Martín-García, R., Villar-Tajadura, M.A., Estravis, M., Coll, P.M., and Pérez, P. (2016).
Rga6 is a Fission Yeast Rho GAP Involved in Cdc42 Regulation of Polarized Growth.
Mol Biol. Cell. 27:1524-1535
Cortés,J.C.G., Pujol, N., Sato, M., Pinar, M., Ramos,M., Moreno, M.B., Osumi, M., Ribas, Jc., and Pérez, P. (2015).
Cooperation between Paxillin-like Protein Pxl1 and Glucan Synthase Bgs1 Is Essential for Actomyosin Ring Stability and Septum Formation in Fission Yeast,
PLoS Genet. 11 Issue: 7 Pages: e1005358
Madrid, M., Jimenez R., Sánchez-Mir, L., Franco, A., Soto, T., Vicente-Soler, J., Gacto, M., Pérez, P. and Cansado, J. (2015).
Multiple regulatory levels influence cell integrity control by PKC ortholog Pck2 in fission yeast.
J. Cell Sci. 128:266-280.
Martín-García, R., Coll, P.M., and Pérez, P. (2014).
F-BAR domain protein Rga7 collaborates with Cdc15 and Imp2 to ensure proper cytokinesis in fission yeast.
J. Cell Sci. 127:4146-4158
Research grants
MINECO BIO2015-69958-P
Links of interest