Hypotonic shock mediation by p38 MAPK, JNK, PKC, FAK, OSR1 and SPAK in osmosensing chloride secreting cells of killifish opercular epithelium

Marshall, William S.; Ossum, Carlo G.; Hoffmann, Else K.

doi:10.1242/jeb.01491

Cited by 110 publications

(80 citation statements)

References 71 publications

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“…Fish regulate cell volume by activating channel-and cotransporter-mediated efflux of osmolytes such as Cl − or K + , allowing water to passively follow (27)(28)(29). Aquaporins are a family of proteins that facilitate passage of water molecules across biological membranes.…”

Section: Resultsmentioning

confidence: 99%

Genomic mechanisms of evolved physiological plasticity in killifish distributed along an environmental salinity gradient

Whitehead

Roach

Zhang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

195

224

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Adaptive variation tends to emerge clinally along environmental gradients or discretely among habitats with limited connectivity. However, in Atlantic killifish (Fundulus heteroclitus), a population genetic discontinuity appears in the absence of obvious barriers to gene flow along parallel salinity clines and coincides with a physiologically stressful salinity. We show that populations resident on either side of this discontinuity differ in their abilities to compensate for osmotic shock and illustrate the physiological and functional genomic basis of population variation in hypoosmotic tolerance. A population native to a freshwater habitat, upstream of the genetic discontinuity, exhibits tolerance to extreme hypoosmotic challenge, whereas populations native to brackish or marine habitats downstream of the discontinuity lose osmotic homeostasis more severely and take longer to recover. Comparative transcriptomics reveals a core transcriptional response associated with acute and acclimatory responses to hypoosmotic shock and posits unique mechanisms that enable extreme osmotic tolerance. Of the genes that vary in expression among populations, those that are putatively involved in physiological acclimation are more likely to exhibit nonneutral patterns of divergence between freshwater and brackish populations. It is not the well-known effectors of osmotic acclimation, but rather the lesser-known immediateearly responses, that appear important in contributing to population differences.adaptive acclimation | ecological genomics | microarray A tlantic killifish (Fundulus heteroclitus) occupy an extremely wide osmotic niche from freshwater to marine, and populations are distributed along steep salinity gradients in Atlantic coast estuaries. In the Chesapeake Bay, salinity gradients are distributed across hundreds of kilometers, although no obvious barriers to gene flow exist across this continuum of osmotic habitats. Because salinity is arguably the most important single physical environmental variable that delimits aquatic species distributions in nature (including Fundulus species; ref. 1), we exploit F. heteroclitus distributed along Chesapeake Bay salinity gradients as a model to discover genes and pathways that enable extreme physiological plasticity and to explore the physiological and functional genomic basis of adaptive microevolution in alternative osmotic environments.Results and Discussion Population Genetic Divergence. We characterized the genetic structure of killifish distributed along two parallel salinity gradients in Chesapeake Bay: one along the Potomac River and the other along the James River (Fig. 1A). Steep clines in allele frequency for both mitochondrial and nuclear markers were centered at nearly identical salinities along the parallel gradients (Fig. 1B). Genotype frequency clines bounded the tidal freshwater transition region (<0.5 ppt) of both rivers, where sites upstream are freshwater year-round according to 20 y of data logged from fixed monitoring stations (www.chesapeakebay.net/ data_...

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Section: Resultsmentioning

confidence: 99%

Genomic mechanisms of evolved physiological plasticity in killifish distributed along an environmental salinity gradient

Whitehead

Roach

Zhang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

195

224

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“…The p38 MAPK pathway, previously shown to negatively regulate malignant cell growth and tumorigenesis by inducing G2-M cell cycle arrest and apoptosis (Han and Sun 2007), can be activated by various external stimuli such as bacterial infection, inflammatory cytokines, and UV radiation. Because osmotic shock also potently induces p38 MAPK activation through dual tyrosine/threonine phosphorylation mediated by two upstream MAPK kinases (MEKs), MEK3 and MEK6 (Marshall et al 2005), we wondered whether the cell volume increase in the EAG2-depleted cells, which mimics the cellular outcome of hypotonic stress, would lead to p38 MAPK pathway activation, thereby causing G2 cell cycle arrest and suppression of tumor growth.…”

Section: Eag2 Knockdown Results In a Striking Increase In Cell Volumementioning

confidence: 99%

Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics

et al. 2012

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Medulloblastoma (MB) is the most common pediatric CNS malignancy. We identify EAG2 as an overexpressed potassium channel in MBs across different molecular and histological subgroups. EAG2 knockdown not only impairs MB cell growth in vitro, but also reduces tumor burden in vivo and enhances survival in xenograft studies. Mechanistically, we demonstrate that EAG2 protein is confined intracellularly during interphase but is enriched in the plasma membrane during late G2 phase and mitosis. Disruption of EAG2 expression results in G2 arrest and mitotic catastrophe associated with failure of premitotic cytoplasmic condensation. While the tumor suppression function of EAG2 knockdown is independent of p53 activation, DNA damage checkpoint activation, or changes in the AKT pathway, this defective cell volume control is specifically associated with hyperactivation of the p38 MAPK pathway. Inhibition of the p38 pathway significantly rescues the growth defect and G2 arrest. Strikingly, ectopic membrane expression of EAG2 in cells at interphase results in cell volume reduction and mitotic-like morphology. Our study establishes the functional significance of EAG2 in promoting MB tumor progression via regulating cell volume dynamics, the perturbation of which activates the tumor suppressor p38 MAPK pathway, and provides clinical relevance for targeting this ion channel in human MBs.

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“…For instance, phospholipase C (PLC) and mitogen-activated protein kinase (MAPK) signaling pathways are involved in osmosensing in tilapia (Loretz et al, 2004). MAPK pathways also play a role in osmosensing in killifish and turbot (Kültz and Avila, 2001;Marshall et al, 2005). Reversible protein phosphorylation provides a link between cytoskeletal strain and osmosensory signal transduction during salinity stress.…”

Section: Evolution Of High Salinity Tolerance In Euryhaline Fishesmentioning

confidence: 99%

“…This link is exemplified by myosin light chain kinase (MLCK), which phosphorylates a tight junction protein, causes F-actin distribution, and is required for hyperosmotic activation of Na + /Cl − /taurine co-transporters in primary cultures of Japanese eel gill cells (Chow et al, 2009). Moreover, focal adhesion kinase (FAK) is dephosphorylated in response to hypo-osmotic stress in killifish gill and opercular epithelia (Marshall et al, 2005). FAK dephosphorylation has been shown to regulate the activity of Na + /K + /2Cl -co-transporter (NKCC) and cystic fibrosis transmembrane conductance regulator (CTFR) transport proteins during salinity stress (Marshall et al, 2008(Marshall et al, , 2009.…”

Section: Evolution Of High Salinity Tolerance In Euryhaline Fishesmentioning

confidence: 99%

Physiological mechanisms used by fish to cope with salinity stress

Kültz

2015

Journal of Experimental Biology

324

161

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Salinity represents a critical environmental factor for all aquatic organisms, including fishes. Environments of stable salinity are inhabited by stenohaline fishes having narrow salinity tolerance ranges. Environments of variable salinity are inhabited by euryhaline fishes having wide salinity tolerance ranges. Euryhaline fishes harbor mechanisms that control dynamic changes in osmoregulatory strategy from active salt absorption to salt secretion and from water excretion to water retention. These mechanisms of dynamic control of osmoregulatory strategy include the ability to perceive changes in environmental salinity that perturb body water and salt homeostasis (osmosensing), signaling networks that encode information about the direction and magnitude of salinity change, and epithelial transport and permeability effectors. These mechanisms of euryhalinity likely arose by mosaic evolution involving ancestral and derived protein functions. Most proteins necessary for euryhalinity are also critical for other biological functions and are preserved even in stenohaline fish. Only a few proteins have evolved functions specific to euryhaline fish and they may vary in different fish taxa because of multiple independent phylogenetic origins of euryhalinity in fish. Moreover, proteins involved in combinatorial osmosensing are likely interchangeable. Most euryhaline fishes have an upper salinity tolerance limit of approximately 2× seawater (60 g kg −1). However, some species tolerate up to 130 g kg −1 salinity and they may be able to do so by switching their adaptive strategy when the salinity exceeds 60 g kg −1. The superior salinity stress tolerance of euryhaline fishes represents an evolutionary advantage favoring their expansion and adaptive radiation in a climate of rapidly changing and pulsatory fluctuating salinity. Because such a climate scenario has been predicted, it is intriguing to mechanistically understand euryhalinity and how this complex physiological phenotype evolves under high selection pressure.

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Hypotonic shock mediation by p38 MAPK, JNK, PKC, FAK, OSR1 and SPAK in osmosensing chloride secreting cells of killifish opercular epithelium

Cited by 110 publications

References 71 publications

Genomic mechanisms of evolved physiological plasticity in killifish distributed along an environmental salinity gradient

Genomic mechanisms of evolved physiological plasticity in killifish distributed along an environmental salinity gradient

Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics

Physiological mechanisms used by fish to cope with salinity stress

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