Abstract

The budding yeast Saccharomyces cerevisiae has an actin cytoskeleton that comprises a set of protein components analogous to those found in the actin cytoskeletons of higher eukaryotes. Furthermore, the actin cytoskeletons of S. cerevisiae and of higher eukaryotes have some similar physiological roles. The genetic tractability of budding yeast and the availability of a stable haploid cell type facilitates the application of molecular genetic approaches to assign functions to the various actin cytoskeleton components. This has provided information that is in general complementary to that provided by studies of the equivalent proteins of higher eukaryotes and hence has enabled a more complete view of the role of these proteins. Several human functional homologues of yeast actin effectors are implicated in diseases. A better understanding of the molecular mechanisms underpinning the functions of these proteins is critical to develop improved therapeutic strategies. In this article we chose as examples four evolutionarily conserved proteins that associate with the actin cytoskeleton: (1) yeast Hof1p/mammalian PSTPIP1, (2) yeast Rvs167p/mammalian BIN1, (3) yeast eEF1A/eEF1A1 and eEF1A2 and (4) yeast Yih1p/mammalian IMPACT. We compare the knowledge on the functions of these actin cytoskeleton-associated proteins that has arisen from studies of their homologues in yeast with information that has been obtained from in vivo studies using live animals or in vitro studies using cultured animal cell lines.

Highlights

  • It is clear that the actin cytoskeleton plays a key role in diverse cellular processes including control of cell morphology and division, and processes like protein translation and cellular metabolism

  • Given the complexity associated with the function of the actin cytoskeleton, the ability to employ powerful molecular genetic approaches becomes crucial to characterize the specific contribution made by each actin cytoskeleton component to the various different cellular processes it may influence

  • Model eukaryotes that are amenable to molecular genetic modification provide the researcher with the capacity to employ molecular genetic approaches to gain novel insights into the function of the actin cytoskeleton at the level of individual molecules

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Summary

Yeast as a Model Organism

Budding yeast (Saccharomyces cerevisiae) is a popular experimental model organism for the study of cellular processes. As well as genome-wide collections of gene knock-out and regulated knock-down mutant strains there are fluorescently-tagged versions of most S. cerevisiae gene products and these have been used to create a database of the subcellular localization patterns and protein abundance under different environmental conditions of most S. cerevisiae gene products [10,11]. The ability to combine classical genetic, molecular biology, biochemical and cell biology approaches using the same organism (as described above) as well as the existence of an actin cytoskeleton with components conserved between yeast and humans have made S. cerevisiae a good experimental model for study of the actin cytoskeleton and actin-dependent cellular processes [28,29,30,31,32,33,34,35]. Before discussing these actin cytoskeleton proteins in detail, it is necessary to first give a brief introduction to the yeast actin cytoskeleton and review its structure, assembly and cellular roles

Actin Cytoskeleton in Yeast
Polarization of the Actin Cytoskeleton during the Budding Cycle of Yeast
Role of Septins in Defining the Nascent Bud Site and Bud Neck in Yeast
Formation of Cortical Actin Patches and Their Function in Endocytosis
Overview of Cytokinesis in Yeast and Mammals
Initiation of Actomyosin Contractile Ring Assembly in Yeast
Role of the Formins Bni1p and Bnr1p in Actomyosin Ring Assembly in Yeast
Contraction of the Actomyosin Ring
1.10. Septum Formation during Cytokinesis in Yeast
1.11. Septum Degradation and Cell Separation in Yeast
Budding Yeast Hof1p and Human PSTPIP1
Schematic
Links between Actin and Translation
Gcn2 Function
Gcn2 is an Important Sensor of the State of the Actin Cytoskeleton
The GCN2-Actin Regulatory Axis May Have a Wide-Reaching Relevance
The AMPH1 and BIN1 Human Amphiphysins and Their Link to Actin Cytoskeleton
Cancer
Centronuclear Myopathies
Alzheimer’s Disease
Concluding Remarks and Future Directions
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