Hydrostatic Pressure Sensing by WNK kinases

Humphreys, John F.; Teixeira, Liliana R.; Akella, Radha; He, Huixin; Kannangara, Ashari Rashmi; Sekulski, Kamil; Pleinis, John M.; Liwocha, Joanna; Jiou, Jenny; Servage, Kelly A.; Orth, Kim; Joachimiak, Łukasz A.; Rizo, Josep; Cobb, Melanie H.; Brautigam, Chad A.; Rodan, Aylin R.; Goldsmith, Elizabeth J.

doi:10.1091/mbc.e23-03-0113

Cited by 3 publications

(2 citation statements)

References 59 publications

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“…The recently observed sensation of hydrostatic pressure by WNK3 in HEK293 cells and Malpighian tubules of Drosophila melanogaster provisionally suggests an analog involvement of WNKs in sensation of bladder filling. 75 Storage symptoms in OAB may be caused by aberrant sensation of hydrostatic pressure during bladder filling, or by uncontrolled voiding contractions of the detusor. Storage symptoms often occur together with voiding symptoms, also as a consequence of chronic incomplete bladder emptying in BPH, but again need separate medical treatment, so that WNKs merit further consideration in lower urinary tract symptoms.…”

Section: Discussionmentioning

confidence: 99%

Isoform‐independent promotion of contractility and proliferation, and suppression of survival by with no lysine/K kinases in prostate stromal cells

Liu,

Huang,

Wang

et al. 2024

The FASEB Journal

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With no lysine/K kinases (WNKs) promote vasocontraction and vascular smooth muscle cell proliferation. In the prostate, smooth muscle contraction and growth may be critical for the development and medical treatment of voiding symptoms in benign prostatic hyperplasia. Here, we examined the effects of isoform‐specific WNK silencing and of the WNK inhibitor WNK463 on growth‐related functions and contraction in prostate stromal cells, and in human prostate tissues. Impacts of WNK silencing by transfection of cultured stromal cells with isoform‐specific siRNAs were qualitatively and quantitatively similar for each WNK isoform. Effects of silencing were largest on cell death (3–5 fold increase in annexin V‐positive/7‐AAD‐positive cells), on proliferation rate, Ki‐67 mRNA expression and actin organization (reduced around two‐thirds). Contraction in matrix contraction assays and viability were reduced to a lower degree (approximately half), but again to a similar extent for each WNK isoform. Effects of silencing were quantitatively and qualitatively reproduced by 10 μM WNK463, while 1 μM still induced cell death and breakdown in actin organization, without affecting proliferation or viability. Using 500 nM and 10 μM, WNK463 partly inhibited neurogenic and U46619‐induced contractions of human prostate tissues (around half), while inhibition of α1‐adrenergic contractions (around half) was limited to 10 μM. All four WNK isoforms suppress cell death and promote proliferation in prostate stromal cells. WNK‐driven contraction of stromal cells appears possible, even though to a limited extent. Outcomes of isoform‐specific WNK silencing can be fully reproduced by WNK463, including inhibition of smooth muscle contraction in human prostate tissues, but require high concentrations.

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Section: Discussionmentioning

confidence: 99%

Isoform‐independent promotion of contractility and proliferation, and suppression of survival by with no lysine/K kinases in prostate stromal cells

Liu,

Huang,

Wang

et al. 2024

The FASEB Journal

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“…When luminal fluid flow decreases, cell volume may increase, activating mechanosensation and recruiting additional directional ion transport. MTs of insects have recently been shown to react to changes in hydrostatic pressure ( 120 ). Ligand-gated ion channels have similarly been detected in the MTs of multiple insect clades (e.g., 121 , 122 ) and epithelial V m can change in response to stimulation of neurotransmitters and endocrine ligands.…”

Section: Discussionmentioning

confidence: 99%

Voltage-gated ion channels as novel regulators of epithelial ion transport in the osmoregulatory organs of insects

Dates,

Kolosov

2024

Front. Insect Sci.

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Voltage-gated ion channels (VGICs) respond to changes in membrane potential (Vm) and typically exhibit fast kinetic properties. They play an important role in signal detection and propagation in excitable tissues. In contrast, the role of VGICs in non-excitable tissues like epithelia is less studied and less clear. Studies in epithelia of vertebrates and invertebrates demonstrate wide expression of VGICs in epithelia of animals. Recently, VGICs have emerged as regulators of ion transport in the Malpighian tubules (MTs) and other osmoregulatory organs of insects. This mini-review aims to concisely summarize which VGICs have been implicated in the regulation of ion transport in the osmoregulatory epithelia of insects to date, and highlight select groups for further study. We have also speculated on the roles VGICs may potentially play in regulating processes connected directly to ion transport in insects (e.g., acid-base balance, desiccation, thermal tolerance). This review is not meant to be exhaustive but should rather serve as a thought-provoking collection of select existing highlights on VGICs, and to emphasize how understudied this mechanism of ion transport regulation is in insect epithelia.

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Macromolecular condensation buffers intracellular water potential

Watson,

Seinkmane,

Styles

et al. 2023

Nature

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Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular interactions1. Reciprocally, macromolecules restrict the movement of ‘structured’ water molecules within their hydration layers, reducing the available ‘free’ bulk solvent and therefore the total thermodynamic potential energy of water, or water potential. Here, within concentrated macromolecular solutions such as the cytosol, we found that modest changes in temperature greatly affect the water potential, and are counteracted by opposing changes in osmotic strength. This duality of temperature and osmotic strength enables simple manipulations of solvent thermodynamics to prevent cell death after extreme cold or heat shock. Physiologically, cells must sustain their activity against fluctuating temperature, pressure and osmotic strength, which impact water availability within seconds. Yet, established mechanisms of water homeostasis act over much slower timescales2,3; we therefore postulated the existence of a rapid compensatory response. We find that this function is performed by water potential-driven changes in macromolecular assembly, particularly biomolecular condensation of intrinsically disordered proteins. The formation and dissolution of biomolecular condensates liberates and captures free water, respectively, quickly counteracting thermal or osmotic perturbations of water potential, which is consequently robustly buffered in the cytoplasm. Our results indicate that biomolecular condensation constitutes an intrinsic biophysical feedback response that rapidly compensates for intracellular osmotic and thermal fluctuations. We suggest that preserving water availability within the concentrated cytosol is an overlooked evolutionary driver of protein (dis)order and function.

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Hydrostatic Pressure Sensing by WNK kinases

Cited by 3 publications

References 59 publications

Isoform‐independent promotion of contractility and proliferation, and suppression of survival by with no lysine/K kinases in prostate stromal cells

Isoform‐independent promotion of contractility and proliferation, and suppression of survival by with no lysine/K kinases in prostate stromal cells

Voltage-gated ion channels as novel regulators of epithelial ion transport in the osmoregulatory organs of insects

Macromolecular condensation buffers intracellular water potential

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