2014
DOI: 10.1038/nchembio.1662
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Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas

Abstract: We identified a Cu accumulating structure with a dynamic role in intracellular Cu homeostasis. During Zn limitation, Chlamydomonas reinhardtii hyperaccumulated Cu, dependent on the nutritional Cu sensor CRR1, but was functionally Cu-deficient. Visualization of intracellular Cu revealed major Cu accumulation sites coincident with electron-dense structures that stained positive for low pH and polyphosphate, suggesting that they are lysosome-related organelles. NanoSIMS showed colocalization of Ca and Cu, and X-r… Show more

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Cited by 153 publications
(203 citation statements)
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“…In the brain, extracellular copper signals may be released directly from the synapse (20). Interestingly, vesicular storage and mobilization of copper has been observed in other systems, including the algae C. reinhardtii, which accumulates copper in acidocalcisomes and mobilizes stored copper under conditions of nutritional copper restriction (94). In mammalian systems, intracellular copper trafficking is influenced by the cell's redox state (95), and changes in redox state may be able to trigger mobilization of copper signals.…”
Section: Resultsmentioning
confidence: 99%
“…In the brain, extracellular copper signals may be released directly from the synapse (20). Interestingly, vesicular storage and mobilization of copper has been observed in other systems, including the algae C. reinhardtii, which accumulates copper in acidocalcisomes and mobilizes stored copper under conditions of nutritional copper restriction (94). In mammalian systems, intracellular copper trafficking is influenced by the cell's redox state (95), and changes in redox state may be able to trigger mobilization of copper signals.…”
Section: Resultsmentioning
confidence: 99%
“…4A). These vacuoles, called acidocalcisomes, are acidified compartments that store polyphosphate complexed with high concentrations of cations, including calcium, iron, zinc, and copper (46)(47)(48). Thus, an alternative candidate for the trans-Golgi filaments is polyphosphate, the major nonorganic component of acidocalcisomes (49)(50)(51).…”
Section: Resultsmentioning
confidence: 99%
“…Encouraged by these findings, we sought to probe loosely bound copper pools in higher neuronal tissue models and study their roles in regulating neural circuits under basal conditions with a molecular imaging approach. However, initial attempts to use CS3 and other available copper indicators to reliably visualize labile copper stores in tissue were unsuccessful, despite their utility in a wide range of cell culture models (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). We speculated that the relative hydrophobicity of BODIPY dyes could potentially limit their utility in thicker biological specimens due to localization and aggregation effects (30,42,43).…”
Section: Significancementioning
confidence: 99%
“…This situation is unsurprising, as the invention of fluorescent probes is a developing technology and not every probe can be used with the same efficacy in every cell type. In particular, the requirement for careful synthesis, purification, and handling of CS3 due to its relatively short shelf life, even in solid form (41), led us to explore alternative sensor platforms for copper detection. To address this technological gap, we designed and synthesized a family of fluorescent copper sensors, Copper Rhodols 1-5 (CR1−5), based on the rhodol scaffold as shown in Fig.…”
Section: Significancementioning
confidence: 99%