Pleiotropic signaling pathways orchestrate yeast development

https://doi.org/10.1016/j.mib.2011.09.004Get rights and content

Developmental phenotypes in Saccharomyces cerevisiae and related yeasts include responses such as filamentous growth, sporulation, and the formation of biofilms and complex colonies. These developmental phenotypes are regulated by evolutionarily conserved, nutrient-responsive signaling networks. The signaling mechanisms that control development in yeast are highly pleiotropic — all the known pathways contribute to the regulation of multiple developmental outcomes. This degree of pleiotropy implies that perturbations of these signaling pathways, whether genetic, biochemical, or environmentally induced, can manifest in multiple (and sometimes unexpected) ways. We summarize the current state of knowledge of developmental pleiotropy in yeast and discuss its implications for understanding functional relationships.

Highlights

► Nutrient stress induces developmental switches in Saccharomyces cerevisiae (baker’s yeast) and related fungi. ► The signaling pathways that control development are highly pleoiotropic. ► Because of signaling pathway pleiotropy, developmental phenotypes can be strongly correlated. ► Pleiotropy can be exploited in functional studies to discover or understand interactions within and between signaling pathways. ► Understanding the causes and consequences of pleiotropy is important in ecological, clinical, and agricultural contexts.

Introduction

In response to stress, the baker’s yeast Saccharomyces cerevisiae and related fungi undergo a variety of developmental switches. These developmental switches include transitions to filamentous growth [1], changes in interactions between cells that lead to biofilms [2••], and architecturally complex colonies 3, 4, or the induction of meiosis and sporulation [5]. These responses are induced by signals that act through a variety of signaling pathways, all of which regulate multiple developmental phenotypes. In this review, we emphasize the pleiotropic nature of developmental pathways in yeast. We consider the implications of pleiotropy for understanding functional relationships among developmental responses and discuss the ecological, industrial, and clinical implications of developmental pleiotropy.

Section snippets

Filamentous growth

Filamentous growth refers to both diploid pseudohyphal growth and haploid invasive growth, both of which are induced by nutrient limitation. Pseudohyphal growth is primarily induced by nitrogen starvation [6], although several reports demonstrate a secondary role for carbon type and quality in its regulation (Figure 1b) 7, 8, 9. The pseudohyphal response is characterized by a switch from bipolar to unipolar budding, incomplete mother-daughter cell separation, and cell elongation. These

Developmental pathways

Genetic and biochemical studies have identified five major signaling pathways [21] that are involved in nutrient-induced developmental responses in yeast: (1) the cAMP-PKA pathway; (2) the TOR pathway; (3) the SNF1/AMPK pathway; (4) the Rim101 pathway; and (5) the Kss1-MAPK pathway. As we discuss below, all these pathways have known or predicted pleiotropic effects on at least two (and in some cases all three) developmental phenotypes.

Combinatorial patterns of pathway activity regulate yeast development

If almost every one of the key signaling pathways regulates multiple developmental phenotypes, often in the same direction, how then do yeast mount appropriate responses in the face of particular nutrient challenges? The answer almost surely lies in combinatorial pathway interactions. The joint effects of multiple signaling pathways and their relative activities are key features of the cellular decision making that leads to different developmental fates in yeast [58]. Recent studies have used

Summary

Yeast, like most microbes, make developmental decisions in response to nutrient cues. Most investigations aimed at understanding the mechanisms that regulate developmental switches in S. cerevisiae have focused on single developmental outcomes, without considering the potential for parallel responses in other phenotypes. As we have outlined above, the gene networks that regulate development in yeast are highly pleiotropic, and thus correlated changes in developmental responses are likely to be

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

We thank Jennifer Reininga and Debra Murray for helpful comments on this manuscript. This work was supported in part by the NIH (P50GM081883-01) and NSF (MCB-0614959).

References (71)

  • S. Piccirillo et al.

    The Rim101p/PacC pathway and alkaline pH regulate pattern formation in yeast colonies

    Genetics

    (2010)
  • G. Pimienta et al.

    Canonical and alternative MAPK signaling

    Cell Cycle

    (2007)
  • H. Saito

    Regulation of cross-talk in yeast MAPK signaling pathways

    Curr Opin Microbiol

    (2010)
  • S. Zaman et al.

    Glucose regulates transcription in yeast through a network of signaling pathways

    Mol Syst Biol

    (2009)
  • P.K. Vinod et al.

    Integration of global signaling pathways, cAMP-PKA, MAPK and TOR in the regulation of FLO11

    PLoS ONE

    (2008)
  • V. Stovícek et al.

    General factors important for the formation of structured biofilm-like yeast colonies

    Fungal Genet Biol

    (2010)
  • S.M. Honigberg et al.

    Signal pathway integration in the switch from the mitotic cell cycle to meiosis in yeast

    J Cell Sci

    (2003)
  • C.J. Gimeno et al.

    Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS

    Cell

    (1992)
  • M.G. Lambrechts et al.

    Muc1, a mucin-like protein that is regulated by Mss10, is critical for pseudohyphal differentiation in yeast

    Proc Natl Acad Sci USA

    (1996)
  • S. Van de Velde et al.

    Cyclic AMP-protein kinase A and Snf1 signaling mechanisms underlie the superior potency of sucrose for induction of filamentation in Saccharomyces cerevisiae

    Eukaryot Cell

    (2008)
  • R.L. Roberts et al.

    Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth

    Genes Dev

    (1994)
  • P.J. Cullen et al.

    Glucose depletion causes haploid invasive growth in yeast

    Proc Natl Acad Sci USA

    (2000)
  • J.H. McCusker et al.

    Saccharomyces cerevisiae virulence phenotype as determined with CD-1 mice is associated with the ability to grow at 42 degrees C and form pseudohyphae

    Infect Immun

    (1994)
  • Z. Palková et al.

    Life within a community: benefit to yeast long-term survival

    FEMS Microbiol Rev

    (2006)
  • L. Hall-Stoodley et al.

    Bacterial biofilms: from the natural environment to infectious diseases

    Nat Rev Microbiol

    (2004)
  • B. Schink

    Energetics of syntrophic cooperation in methanogenic degradation

    Microbiol Mol Biol Rev

    (1997)
  • L. Hall-Stoodley et al.

    Evolving concepts in biofilm infections

    Cell Microbiol

    (2009)
  • T. Coenye et al.

    In vitro and in vivo model systems to study microbial biofilm formation

    J Microbiol Meth

    (2010)
  • Y. Kassir et al.

    Transcriptional regulation of meiosis in budding yeast

    Int Rev Cytol

    (2003)
  • L. Schneper et al.

    Sense and sensibility: nutritional response and signal integration in yeast

    Curr Opin Microbiol

    (2004)
  • J.M. Thevelein et al.

    Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae

    Mol Microbiol

    (1999)
  • S. Zaman et al.

    How Saccharomyces responds to nutrients

    Annu Rev Genet

    (2008)
  • J.S. Stephan et al.

    The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy in Saccharomyces cerevisiae

    Autophagy

    (2010)
  • X. Pan et al.

    Protein kinase A operates a molecular switch that governs yeast pseudohyphal differentiation

    Mol Cell Biol

    (2002)
  • X. Pan et al.

    Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae

    Mol Cell Biol

    (1999)
  • Cited by (0)

    View full text