Calcineurin regulates the yeast synaptojanin Inp53/Sjl3 during membrane stress.
Bottom Line: By activating Inp53, calcineurin repolarizes the actin cytoskeleton and maintains normal plasma membrane morphology in synaptojanin-limited cells.This response has physiological and molecular similarities to calcineurin-regulated activity-dependent bulk endocytosis in neurons, which retrieves a bolus of plasma membrane deposited by synaptic vesicle fusion.We propose that activation of Ca(2+)/calcineurin and PI(4,5)P2 signaling to regulate endocytosis is a fundamental and conserved response to excess membrane in eukaryotic cells.
Affiliation: Department of Biology, Stanford University, Stanford, CA 94305.Show MeSH
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Mentions: Because the altered subcellular distribution of CN likely reflected a change in protein–protein interactions, we sought to identify proteins whose association with CN increased during hyperosmotic stress. Mass spectrometry was used to identify proteins that copurified with endogenously expressed, epitope-tagged CN (Cna2-TEV-ZZ) isolated from either unstressed cells or cells exposed to 1.25 M KCl, as compared with purifications from untagged cells, which controlled for nonspecific background. These analyses suggested a possible interaction between CN and Inp53/Sjl3, one of three yeast synaptojanins (Figure 4A; Srinivasan et al., 1997; Stolz et al., 1998), which was enhanced during hyperosmotic stress. In unstressed cells, Inp53 contributes to protein sorting at the TGN but localizes to actin patches and stimulates repolarization of the actin cytoskeleton during osmotic stress (Ooms et al., 2000). Thus we hypothesized that CN might promote actin polarization during hyperosmotic stress by regulating Inp53.
Affiliation: Department of Biology, Stanford University, Stanford, CA 94305.