Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments

DiPilato, Lisa M.; Cheng, Xiaodong; Zhang, Jin

doi:10.1073/pnas.0405973101

Cited by 415 publications

(411 citation statements)

References 43 publications

(44 reference statements)

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“…Interestingly, in the in vivo situation, intestinal incretins, such as GIP or GLP-1, are thought to act in the same way [21]. Conceivably, in the insulin cells, different cAMP compartments [11] are drawn upon to ensure an optimal insulin response to glucose. Similarly, glucose itself might stimulate the formation of cAMP in a specific compartment in insulin cells of control mice.…”

Section: Discussionmentioning

confidence: 99%

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Secretory and electrophysiological characteristics of insulin cells from gastrectomized mice: Evidence for the existence of insulinotropic agents in the stomach

Salehi

Eliasson

et al. 2007

Regulatory Peptides

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Section: Discussionmentioning

confidence: 99%

“…The role of cAMP in the regulation of glucose-stimulated insulin secretion is not fully understood and experimental results are sometimes contradictory, probably because cAMP acts through several different pathways. In fact, there is evidence for a subcellular compartmentalization of cAMP and cAMP-induced actions [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Secretory and electrophysiological characteristics of insulin cells from gastrectomized mice: Evidence for the existence of insulinotropic agents in the stomach

Salehi

Eliasson

et al. 2007

Regulatory Peptides

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“…And for this same reason, they can be directed to subcellular regions via specific amino acid targeting sequences that are added to the biosensor. Targeting of biosensors to specific locations is important for studying the spatial regulation of signaling dynamics, and, as will be discussed in later sections, represents one proven strategy for the coimaging of FRET-based biosensors (29,31).…”

Section: Genetic Encodabilitymentioning

confidence: 99%

“…This coimaging strategy is useful if the two signaling events of interest occur in distinct subcellular locations, or when asking questions about how a signaling event at one cellular location affects signaling elsewhere in the cell. For instance, DiPilato et al were interested in understanding the precise temporal correlation between cAMP accumulation at the plasma membrane and PKA activity in the nucleus (31). To study this, they targeted the FRET-based Indicator of cAMP Using Epac (ICUE) to the plasma membrane and coexpressed this biosensor with nuclear localized A kinase activity reporter (AKAR).…”

Section: Coimaging Of Signaling Activities Via Physical Separation Ofmentioning

confidence: 99%

Dynamic visualization of signal transduction in living cells: From second messengers to kinases

Herbst

Zhang

2009

IUBMB Life

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SummaryThe study of signal transduction, or the highly regulated series of biochemical events which allow a cell to convert a given stimulus into a functional response, has seen a paradigm shift with a recent explosion in the number of genetically encoded FRET-based biosensors capable of detecting spatial and temporal regulation of various signaling events in living cells. The two classes of biosensors discussed, namely kinase activity and second messenger biosensors, utilize two fluorescent proteins (FP) suitable for FRET and convert a signaling event of interest into a conformational change in the biosensor that can be measured as a change in FRET between the two FPs. Individually, these biosensors have been used to elucidate many complex signal transduction mechanisms in various biological systems. However, it has become increasingly clear that it is often more desirable to study multiple signaling events simultaneously, allowing for precise correlation of the temporal profiles of multiple signaling molecules without the complication of cell to cell variability. With the design of spectrally distinct biosensors and new coimaging strategies, simultaneous imaging of multiple signaling events is not only possible, but has aided in mapping the intricate network of cellular signal transduction cascades. Furthermore, as aberrant signal transduction involving second messengers and kinases is implicated in numerous disease states, it is hopeful that these FRET-based biosensors and coimaging strategies can help to unravel the molecular links between altered signal transduction and certain disease states.2009 IUBMB IUBMB Life, 61(9): 902-908, 2009

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“…Her lab's first independent publication involved developing a sensor to visualize and quantify cAMP dynamics (5).…”

mentioning

confidence: 99%

Illuminating Cellular Signaling

Brownlee¹

2007

ACS Chem. Biol.

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he intracellular environment is an incredibly dynamic place, with new signaling molecules being born, dying, interacting, and transforming every minute. However, the roles and actions of many of a cell's signaling molecules remain a mystery. If researchers could light up the dark and shrouded inner environment of a cell, then they could observe cellular signaling in real time. This goal is the focus of work by Jin Zhang of the Johns Hopkins University School of Medicine in Baltimore and her colleagues. Zhang's team has created several fluorescent sensors that give a visual element to the action of intracellular signaling molecules; as they move inside cells, the sensors allow researchers to track and monitor particular signaling events. By shining this spotlight on cellular signaling molecules, Zhang's work is giving unprecedented insight into signal transduction events inside living cells.In the Family. Zhang was born in 1972 in Beijing, China, to parents who were both engineering professors at Tsinghua University. Her parents encouraged her and her older sister, Qing Zhang, to follow their own interests, including writing stories and reading from the family's personal minilibrary of Chinese literature classics and science fiction books.However, notes Zhang, "Science and engineering run in the family, and the family influence was pretty strong." She recalls many dinner discussions during her childhood that focused on why natural phenomena occur. If her parents couldn't answer her or her sister's questions, they encouraged the children to find solutions in books, through logical thinking, or by experimentation. "It became a fun thing to ask why and look for answers. That got me interested in science as a career," says Zhang.

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Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments

Abstract: FRET ͉ cAMP-dependent protein kinase

Cited by 415 publications

References 43 publications

Secretory and electrophysiological characteristics of insulin cells from gastrectomized mice: Evidence for the existence of insulinotropic agents in the stomach

Secretory and electrophysiological characteristics of insulin cells from gastrectomized mice: Evidence for the existence of insulinotropic agents in the stomach

Dynamic visualization of signal transduction in living cells: From second messengers to kinases

Illuminating Cellular Signaling

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