Aldosterone controls primary cilium length and cell size in renal collecting duct principal cells

Jack

et al. 2021

Front. Cell Dev. Biol.

Primary cilia are small, antenna-like organelles that detect and transduce chemical and mechanical cues in the extracellular environment, regulating cell behavior and, in turn, tissue development and homeostasis. Primary cilia are assembled via intraflagellar transport (IFT), which traffics protein cargo bidirectionally along a microtubular axoneme. Ranging from 1 to 10 μm long, these organelles typically reach a characteristic length dependent on cell type, likely for optimum fulfillment of their specific roles. The importance of an optimal cilia length is underscored by the findings that perturbation of cilia length can be observed in a number of cilia-related diseases. Thus, elucidating mechanisms of cilia length regulation is important for understanding the pathobiology of ciliary diseases. Since cilia assembly/disassembly regulate cilia length, we review the roles of IFT in processes that affect cilia assembly/disassembly, including ciliary transport of structural and membrane proteins, ectocytosis, and tubulin posttranslational modification. Additionally, since the environment of a cell influences cilia length, we also review the various stimuli encountered by renal epithelia in healthy and diseased states that alter cilia length and IFT.

Section: Modulation Of Renal Epithelial Cilia Length and Renal Functionmentioning

confidence: 87%

Intraflagellar Transport Proteins as Regulators of Primary Cilia Length

Jack

et al. 2021

Front. Cell Dev. Biol.

The Journal of Physiology

“…Both aldosterone and blood K + have been shown to drive changes in the architecture of the distal tubule. Aldosterone remodelling of the renal tubule is associated with cellular hypertrophy (Komarynets et al., 2020; Wade et al., 1990) and increased proliferation (Hao et al., 2021). Low blood [K + ] in the setting of a low K + diet leads to lengthening of the DCT and is a mechanism by which total NCC expression increases under conditions of hypokalaemia to help limit K + efflux (Saritas et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

Dietary sodium alters aldosterone's effect on renal sodium transporter expression and distal convoluted tubule remodelling

Mutchler,

Hasan,

Murphy

et al. 2024

Aldosterone is responsible for maintaining volume and potassium homeostasis. Although high salt consumption should suppress aldosterone production, individuals with hyperaldosteronism lose this regulation, leading to a state of high aldosterone despite dietary sodium consumption. The present study examines the effects of elevated aldosterone, with or without high salt consumption, on the expression of key Na+ transporters and remodelling in the distal nephron. Epithelial sodium channel (ENaC) α‐subunit expression was increased with aldosterone regardless of Na+ intake. However, ENaC β‐ and γ‐subunits unexpectedly increased at both a transcript and protein level with aldosterone when high salt was present. Expression of total and phosphorylated Na+Cl− cotransporter (NCC) significantly increased with aldosterone, in association with decreased blood [K+], but the addition of high salt markedly attenuated the aldosterone‐dependent NCC increase, despite equally severe hypokalaemia. We hypothesized this was a result of differences in distal convoluted tubule length when salt was given with aldosterone. Imaging and measurement of the entire pNCC‐positive tubule revealed that aldosterone alone caused a shortening of this segment, although the tubule had a larger cross‐sectional diameter. This was not true when salt was given with aldosterone because the combination was associated with a lengthening of the tubule in addition to increased diameter, suggesting that differences in the pNCC‐positive area are not responsible for differences in NCC expression. Together, our results suggest the actions of aldosterone, and the subsequent changes related to hypokalaemia, are altered in the presence of high dietary Na+. imageKey points Aldosterone regulates volume and potassium homeostasis through effects on transporters in the kidney; its production can be dysregulated, preventing its suppression by high dietary sodium intake. Here, we examined how chronic high sodium consumption affects aldosterone's regulation of sodium transporters in the distal nephron. Our results suggest that high sodium consumption with aldosterone is associated with increased expression of all three epithelial sodium channel subunits, rather than just the alpha subunit. Aldosterone and its associated decrease in blood [K+] lead to an increased expression of Na‐Cl cotransporter (NCC); the addition of high sodium consumption with aldosterone partially attenuates this NCC expression, despite similarly low blood [K+]. Upstream kinase regulators and tubule remodelling do not explain these results.

“…Cell sensitivity to mechanical stimuli increases depending on the length of primary cilia (Spasic & Jacobs, 2017). Aldosterone‐stimulated increase in cell size of renal collecting duct epithelial cells seems to be dependent on the length of primary cilia (Komarynets et al , 2020). Despite of accumulation of these evidence, the mechanisms regulating primary cilium morphology and the physiological significance of alterations in primary cilium morphology have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Circadian oscillation in primary cilium length by clock genes regulates fibroblast cell migration

Nakazato,

Matsuda,

Ijaz

et al. 2023

EMBO Reports

Various mammalian cells have autonomous cellular clocks that are produced by the transcriptional cycle of clock genes. Cellular clocks provide circadian rhythms for cellular functions via transcriptional and cytoskeletal regulation. The vast majority of mammalian cells possess a primary cilium, an organelle protruding from the cell surface. Here, we investigated the little‐known relationship between circadian rhythm and primary cilia. The length and number of primary cilia showed circadian dynamics both in vitro and in vivo. The circadian rhythm of primary cilium length was abolished by SR9011 and Bmal1 knockout. A centrosomal protein, pericentrin, transiently accumulates in centriolar satellites, the base of primary cilia at the shortest cilia phase, and induces elongation of primary cilia at the longest cilia phase in the circadian rhythm of primary cilia. In addition, rhythmic cell migration during wound healing depends on the length of primary cilia and affects the rate of wound healing. Our findings demonstrate that the circadian dynamics of primary cilium length by clock genes control fibroblast migration and could provide new insights into chronobiology.