CFTR Cl– channel functional regulation by phosphorylation of focal adhesion kinase at tyrosine 407 in osmosensitive ion transporting mitochondria rich cells of euryhaline killifish

283

161

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.

Section: Evolution Of High Salinity Tolerance In Euryhaline Fishesmentioning

confidence: 99%

Physiological mechanisms used by fish to cope with salinity stress

Kültz

2015

283

161

“…Leak conductance (G L ) was calculated as an extrapolation of the epithelial conductance (G t ) versus I sc adapted from a previous method (Kültz and Onken, 1993), but instead of using the spontaneous variation of G t and I sc , the epithelia in Ussing chambers were inhibited by application of hypotonic shock (60 mOsm kg −1 reduction of basolateral and apical bathing solutions), a treatment that rapidly inhibits the transcellular pathway of active ion secretion by dephosphorylation of NKCC and CFTR (Marshall et al, 2009(Marshall et al, , 2005.…”

Section: Electrophysiology Theorymentioning

confidence: 99%

Paracellular pathway remodeling enhances sodium secretion by teleost fish in hypersaline environments

Cozzi

Robertson

Spieker

et al. 2015

Self Cite

In vertebrate salt-secreting epithelia, Na + moves passively down an electrochemical gradient via a paracellular pathway. We assessed how this pathway is modified to allow Na + secretion in hypersaline environments. Mummichogs (Fundulus heteroclitus) acclimated to hypersaline [2× seawater (2SW), 64‰] for 30 days developed invasive projections of accessory cells with an increased area of tight junctions, detected by punctate distribution of CFTR (cystic fibrosis transmembrane conductance regulator) immunofluorescence and transmission electron miscroscopy of the opercular epithelia, which form a gill-like tissue rich in ionocytes. Distribution of CFTR was not explained by membrane raft organization, because chlorpromazine (50 μmol l ) did not affect opercular epithelia electrophysiology. Isolated opercular epithelia bathed in SW on the mucosal side had a transepithelial potential (V t ) of +40.1±0.9 mV (N=24), sufficient for passive Na + secretion (Nernst equilibrium voltage≡E Na =+24.11 mV). Opercular epithelia from fish acclimated to 2SW and bathed in 2SW had higher V t of +45.1±1.2 mV (N=24), sufficient for passive Na + secretion (E Na =+40.74 mV), but with diminished net driving force. Bumetanide block of Cl − secretion reduced V t by 45% and 29% in SW and 2SW, respectively, a decrease in the driving force for Na + extrusion. Estimates of shunt conductance from epithelial conductance (G t ) versus short-circuit current (I sc ) plots (extrapolation to zero I sc ) suggested a reduction in total epithelial shunt conductance in 2SW-acclimated fish. In contrast, the morphological elaboration of tight junctions, leading to an increase in accessory-cell-ionocyte contact points, suggests an increase in local paracellular conductance, compensating for the diminished net driving force for Na + and allowing salt secretion, even in extreme salinities.

“…The physiological relevance of this is unclear, but is intriguing because FAK phosphorylation is important for regulation of chloride channels during osmotic compensation in killifish MR cells (Marshall et al, 2009), and cystic fibrosis transmembrane conductance regulator chloride channels are deactivated and downregulated in freshwater (Singer et al, 1998).…”

Section: Ion Transportmentioning

confidence: 99%

Salinity- and population-dependent genome regulatory response during osmotic acclimation in the killifish (Fundulus heteroclitus) gill

Whitehead

Roach

Zhang

et al. 2012

128

SUMMARYThe killifish Fundulus heteroclitus is abundant in osmotically dynamic estuaries and it can quickly adjust to extremes in environmental salinity. We performed a comparative osmotic challenge experiment to track the transcriptomic and physiological responses to two salinities throughout a time course of acclimation, and to explore the genome regulatory mechanisms that enable extreme osmotic acclimation. One southern and one northern coastal population, known to differ in their tolerance to hypo-osmotic exposure, were used as our comparative model. Both populations could maintain osmotic homeostasis when transferred from 32 to 0.4p.p.t., but diverged in their compensatory abilities when challenged down to 0.1p.p.t., in parallel with divergent transformation of gill morphology. Genes involved in cell volume regulation, nucleosome maintenance, ion transport, energetics, mitochondrion function, transcriptional regulation and apoptosis showed population-and salinity-dependent patterns of expression during acclimation. Network analysis confirmed the role of cytokine and kinase signaling pathways in coordinating the genome regulatory response to osmotic challenge, and also posited the importance of signaling coordinated through the transcription factor HNF-4. These genome responses support hypotheses of which regulatory mechanisms are particularly relevant for enabling extreme physiological flexibility. Supplementary material available online at