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Active NON-SBIR/STTR RPGS NIH (US)

Plasma membrane stress response

$3.08M USD

Funder NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
Recipient Organization University of Utah
Country United States
Start Date Aug 01, 2024
End Date Jul 31, 2028
Duration 1,460 days
Number of Grantees 1
Roles Principal Investigator
Data Source NIH (US)
Grant ID 10777524
Grant Description

Project Summary The plasma membrane experiences many cellular and environmental changes in form of increasing or decreasing membrane tension. Events such as cytokinesis, cell differentiation, migration, and metabolic changes all affect volume to surface area ratios and thus plasma membrane tension. Therefore, an increasing number of studies identify changes in membrane

tension as a common signal for the cellular status. This signal affects cytoskeleton, ion channels, and cell signaling and thus is able to coordinate cellular response pathways. A goal of cellular stress response is to reestablish normal membrane tension, which is important to maintain cell integrity and functionality of systems associated with the plasma membrane. How eukaryotic cells

sense and maintain membrane tension is poorly understood. We started to address these questions by analyzing the response of yeast Saccharomyces cerevisiae to dramatic changes in osmolarity of the growth medium, a stress that is commonly encountered in the natural environment of this unicellular organism. Within seconds, osmotic stress can change the surface

area of yeast by +/-20%, a change that suggests rapid addition or removal of membrane to/from the surface. Our data indicate that this rapid membrane flux is mediated by the ER-plasma membrane contact sites (EPCS). Current models implicate the EPCS in the shuttling of lipids between the two membranes, a transport activity that can explain our observations during cell

shrinking. However, rapid cell expansion seems to require an additional mechanism, the fusion of the ER with the plasma membrane at contact sites. This proposed fusion allows not only for rapid membrane transport to the plasma membrane, but it also might be able to deliver within seconds stress-response proteins from the ER to the cell surface.

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University of Utah

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