Calcineurin regulates the yeast synaptojanin Inp53/Sjl3 to promote membrane recovery during hyperosmotic stress [electronic resource]
- Guiney, Evan Lloyd.
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- In response to hyperosmotic shock, cells of the budding yeast Saccharomyces cerevisiae lose up to 50% of their volume. This drastic decrease in cell size results in excess plasma membrane, which forms large infoldings that must be quickly removed. How these plasma membrane invaginations are resolved to restore the cell surface is not well understood. We show that hyperosmotic shock activates calcineurin, the Ca2+/calmodulin-dependent protein phosphatase, leading to restoration of normal membrane morphology. During hyperosmotic stress, actin patches (sites of endocytosis) become depolarized; we find that under these conditions calcineurin accumulates at sites of polarized growth and promotes actin patch repolarization. Hyperosmotic stress causes calcineurin to bind to the yeast synaptojanin Inp53/Sjl3 and dephosphorylate its proline rich tail. Dephosphorylation by calcineurin activates Inp53, which in turn dephosphorylates PI(4,5)P2 at the plasma membrane and promotes repolarization of the actin cytoskeleton. Consistently, cells lacking the partially redundant synaptojanins Inp51/Sjl1 and Inp52/Sjl2 require calcineurin for growth even in the absence of hyperosmotic stress, and display abnormal plasma membrane morphology when calcineurin activation of Inp53 is blocked. Finally, we find that calcineurin binding to Inp53 stimulates its association with the yeast amphiphysin Rvs167, suggesting model where calcineurin stimulates Inp53 and Rvs167 mediated membrane scission, promoting recovery from excess membrane stress and allowing resumption of polarized growth. In neurons, periods of intense synaptic vesicle release also result in excess membrane, and calcineurin stimulates association of synaptojanin with amphiphysin to promote synaptic vesicle endocytosis. Our findings in yeast suggest that stimulation of endocytic complex formation by Ca2+/calcineurin is a fundamental and conserved feature of the eukaryotic response to excess plasma membrane.
- Publication date
- Evan Lloyd Guiney.
- Submitted to the Department of Biology.
- Ph.D. Stanford University 2013