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: Under many environmental conditions, CN ensures cell survival by activating the Crz1 transcription factor, promoting its translocation from the cytosol to the nucleus (Stathopoulos and Cyert, 1997; Stathopoulos-Gerontides et al., 1999). Therefore we measured CN-Crz1–dependent expression of 4x-CDRE-LacZ, a reporter gene controlled by the Crz1- binding site, during hyperosmotic stress. As expected, addition of CaCl2 caused a 40-fold induction of CDRE-LacZ expression (Figure 2). In contrast, no activation of CN-Crz1 signaling was observed in response to hyperosmotic stress despite the increase in intracellular Ca2+ that occurs under these conditions (Denis and Cyert, 2002). Instead, hyperosmotic stress blocked Ca2+-dependent activation of Crz1 (Figure 2). This surprising effect suggested that hypertonic conditions inhibit CN/Crz1 signaling, perhaps in part by relocalizing CN and preventing its access to Crz1.
Affiliation: Department of Biology, Stanford University, Stanford, CA 94305.