Let it stick: Strategies and applications for intracellular plasma membrane targeting of proteins in Saccharomyces cerevisiae

• Published in: Yeast (Chichester, England) England), 2024-05, Vol.41 (5), p.315-329
• Main Authors: Muth, Liv Teresa, Van Bogaert, Inge Noëlle Adriënne
• Format: Article
• Language: English
• Subjects: applied research; Cell Membrane - metabolism; Homology; Intracellular; Kinases; lipid binding domains; Lipid Metabolism; Lipids; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metabolic engineering; Myristoylation; Palmitoylation; Plasma; plasma membrane; Pleckstrin; prenylation; Protein Transport; Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Translation; Yeast; yeasts
• ISSN: 0749-503X; 1097-0061; 1097-0061
• DOI: 10.1002/yea.3933

Lipid binding domains and protein lipidations are essential features to recruit proteins to intracellular membranes, enabling them to function at specific sites within the cell. Membrane association can also be exploited to answer fundamental and applied research questions, from obtaining insights into the understanding of lipid metabolism to employing them for metabolic engineering to redirect fluxes. This review presents a broad catalog of membrane binding strategies focusing on the plasma membrane of Saccharomyces cerevisiae. Both lipid binding domains (pleckstrin homology, discoidin‐type C2, kinase associated‐1, basic‐rich and bacterial phosphoinositide‐binding domains) and co‐ and post‐translational lipidations (prenylation, myristoylation and palmitoylation) are introduced as tools to target the plasma membrane. To provide a toolset of membrane targeting modules, respective candidates that facilitate plasma membrane targeting are showcased including their in vitro and in vivo properties. The relevance and versatility of plasma membrane targeting modules are further highlighted by presenting a selected set of use cases. Intracellular plasma membrane targeting of proteins in Saccharomyces cerevisiae can be facilitated by recognizing the headgroups of lipid species through a distinct structural fold, general membrane properties such as charge through patches of basic amino acids or through attachment to respectively insertion into the plasma membrane by amphipathic α‐helices or co‐ and post‐translational lipidations (left site). Plasma membrane binding motifs can be used for a variety of applications in fundamental and applied research (right site). Take‐away Lipid binding domains and co‐ and post‐translational modifications facilitate membrane association through different means and can be employed to target proteins of interest to the plasma membrane in yeast. This review shows various strategies to target the plasma membrane in Saccharomyces cerevisiae that can be used to answer a wide set of fundamental and applied research questions. Verified candidate modules including their specific boundaries that target fluorescent reporters to the plasma membrane serve as a toolbox for researchers that aim to anchor proteins of interest to the plasma membrane.