To investigate the contribution of ion channels to ciliogenesis, we carried out a small interfering RNA (siRNA)-based reverse genetics screen of all ion channels in the mouse genome in murine inner medullary collecting duct kidney cells. This screen revealed four candidate ion channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4. We show that these four ion channels localize to renal tubules, specifically to the base of primary cilia. We report that human KCNQ1 Long QT syndrome disease alleles regulate renal ciliogenesis; KCNQ1-p.R518X, -p.A178T and -p.K362R could not rescue ciliogenesis after Kcnq1-siRNA-mediated depletion in contrast to wild-type KCNQ1 and benign KCNQ1-p.R518Q, suggesting that the ion channel function of KCNQ1 regulates ciliogenesis. In contrast, we demonstrate that the ion channel function of KCNJ10 is independent of its effect on ciliogenesis. Our data suggest that these four ion channels regulate renal ciliogenesis through the periciliary diffusion barrier or the ciliary pocket, with potential implication as genetic contributors to ciliopathy pathophysiology. The new functional roles of a subset of ion channels provide new insights into the disease pathogenesis of channelopathies, which might suggest future therapeutic approaches.
Transient receptor potential channel 1 (TRPC1) is a widely expressed mechanosensitive ion channel located within the endoplasmic reticulum membrane, crucial for refilling depleted internal calcium stores during activation of calcium-dependent signaling pathways. Here, we demonstrate that TRPC1 activity is protective within cartilage homeostasis in the prevention of cellular senescence associated cartilage breakdown during mechanical and inflammatory challenge. We reveal that TRPC1 loss is associated with early stages of osteoarthritis (OA) and plays a non-redundant role in calcium signaling in chondrocytes.
Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia.
Elevated inflammatory reactions are a significant component in cerebral ischemia-reperfusion injury (CIRI). Activation of α7-Nicotinic Acetylcholine Receptor (α7nAChR) reduces stroke-induced inflammation in rats, but the anti-inflammatory pathway in microglia under CIRI condition remains unclear. This study employed qRT-PCR, protein assays, NanoString analysis, and bioinformatics to examine the effects of PNU282987 treatment (α7nAChR agonist) on BV2 microglial functional differentiation in oxygen-glucose deprivation/reoxygenation (OGDR) condition.
To encode continuous sound stimuli, the inner hair cell (IHC) ribbon synapses utilize calcium-binding proteins (CaBPs), which reduce the inactivation of their Ca1.3 calcium channels. Mutations in the gene underlie non-syndromic autosomal recessive hearing loss DFNB93.
Psoriasis is a multifactorial immune-mediated inflammatory disease. Its pathogenesis involves abnormal accumulation of neutrophils and T-cell-related abnormalities. Pyroptosis is a type of regulated cell death associated with innate immunity, but its role in psoriasis is unclear.
MS4A (membrane-spanning 4-domain, subfamily A) molecules are categorized into tetraspanins, which possess four-transmembrane structures. To date, eighteen MS4A members have been identified in humans, whereas twenty-three different molecules have been identified in mice. MS4A proteins are selectively expressed on the surfaces of various immune cells, such as B cells (MS4A1), mast cells (MS4A2), macrophages (MS4A4A), Foxp3CD4 regulatory T cells (MS4A4B), and type 3 innate lymphoid cells (TMEM176A and TMEM176B).
