Increasing the expression of calcium-permeable TRPC3 and TRPC7 channels enhances constitutive secretion

Lavender, Verna; Chong, Setareh; Ralphs, Katherine L.; Wolstenholme, Adrian J.; Reaves, Barbara J.

doi:10.1042/bj20071488

Cited by 27 publications

(9 citation statements)

References 49 publications

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“…ASM cells express a variety of TRPC channels, with TRPC3 being particularly important for modulating Ca 2+ entry and in airway responses to inflammation (Amrani, 2007; Sweeney et al, 2002; Vohra et al, 2013; White et al, 2006). In non-neuronal cells, TRPC3 regulates secretion (Kim et al, 2011; Lavender et al, 2008). In a recent study, using DNA constructs to produce GFP-tagged BDNF, and real-time fluorescence imaging, we showed that vesicular BDNF release occurs in human ASM cells, and is regulated by TRPC3 (Vohra et al, 2013).…”

Section: Bdnf In the Lungmentioning

confidence: 99%

Brain-derived neurotrophic factor in the airways

Prakash

Martin

2014

Pharmacology & Therapeutics

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In addition to their well-known roles in the nervous system, there is increasing recognition that neurotrophins such as brain derived neurotrophic factor (BDNF) as well as their receptors are expressed in peripheral tissues including the lung, and can thus potentially contribute to both normal physiology and pathophysiology of several diseases. The relevance of this family of growth factors lies in emerging clinical data indicating altered neurotrophin levels and function in a range of diseases including neonatal and adult asthma, sinusitis, influenza, and lung cancer. The current review focuses on 1) the importance of BDNF expression and signaling mechanisms in early airway and lung development, critical to both normal neonatal lung function and also its disruption in prematurity and insults such as inflammation and infection; 2) how BDNF, potentially derived from airway nerves modulate neurogenic control of airway tone, a key aspect of airway reflexes as well as dysfunctional responses to allergic inflammation; 3) the emerging idea that local BDNF production by resident airway cells such as epithelium and airway smooth muscle can contribute to normal airway structure and function, and to airway hyperreactivity and remodeling in diseases such as asthma. Furthermore, given its pleiotropic effects in the airway, BDNF may be a novel and appealing therapeutic target.

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Section: Bdnf In the Lungmentioning

confidence: 99%

Brain-derived neurotrophic factor in the airways

Prakash

Martin

2014

Pharmacology & Therapeutics

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“…Although activation of many other vesicular TRPs (Fig. 1) has not been reported, some of them, for example, TRPC3 and TRPC7, have been shown to actively participate in trafficking/exocytosis (Lavender et al. 2008).…”

Section: Trp Channels In the Biosynthetic/secretory Pathwaymentioning

confidence: 99%

TRP channels of intracellular membranes

Dong

Wang

2010

Journal of Neurochemistry

152

176

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J. Neurochem. (2010) 113, 313–328. Abstract Ion channels are classically understood to regulate the flux of ions across the plasma membrane in response to a variety of environmental and intracellular cues. Ion channels serve a number of functions in intracellular membranes as well. These channels may be temporarily localized to intracellular membranes as a function of their biosynthetic or secretory pathways, i.e., en route to their destination location. Intracellular membrane ion channels may also be located in the endocytic pathways, either being recycled back to the plasma membrane or targeted to the lysosome for degradation. Several channels do participate in intracellular signal transduction; the most well known example is the inositol 1,4,5‐trisphosphate receptor (IP3R) in the endoplasmic reticulum. Some organellar intracellular membrane channels are required for the ionic homeostasis of their residing organelles. Several newly‐discovered intracellular membrane Ca2+ channels actually play active roles in membrane trafficking. Transient receptor potential (TRP) proteins are a superfamily (28 members in mammal) of Ca2+‐permeable channels with diverse tissue distribution, subcellular localization, and physiological functions. Almost all mammalian TRP channels studied thus far, like their ancestor yeast TRP channel (TRPY1) that localizes to the vacuole compartment, are also (in addition to their plasma membrane localization) found to be localized to intracellular membranes. Accumulated evidence suggests that intracellularly‐localized TRP channels actively participate in regulating membrane traffic, signal transduction, and vesicular ion homeostasis. This review aims to provide a summary of these recent works. The discussion will also be extended to the basic membrane and electrical properties of the TRP‐residing compartments.

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“…Relevant to airway disease, inflammatory cytokines such as TNFα increase TRPC3 expression [32, 33] while BDNF modulates TRPC3 function in human ASM [6]. In non-neuronal cells, [34, 35] TRPC3 has been shown to regulate secretion, but its non-SOCE role in ASM is not known. Accordingly, in the present study, we hypothesized that TRPC3 is important in BDNF secretion by ASM, and tested this hypothesis in human ASM in the context of enhanced BDNF secretion in the presence of inflammation.…”

Section: Introductionmentioning

confidence: 99%

TRPC3 regulates release of brain-derived neurotrophic factor from human airway smooth muscle

Vohra

Thompson

Sathish

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Exogenous brain-derived neurotrophic factor (BDNF) enhances Ca2+ signaling and cell proliferation in human airway smooth muscle (ASM), especially with inflammation. Human ASM also expresses BDNF, raising the potential for autocrine/paracrine effects. The mechanisms by which ASM BDNF secretion occurs are not known. Transient receptor potential channels (TRPCs) regulate a variety of intracellular processes including store-operated Ca2+ entry (SOCE; including in ASM) and secretion of factors such as cytokines. In human ASM, we tested the hypothesis that TRPC3 regulates BDNF secretion. At baseline, intracellular BDNF was present, and BDNF secretion was detectable by ELISA of cell supernatants or by real-time fluorescence imaging of cells transfected with GFP-BDNF vector. Exposure to the pro-inflammatory cytokine TNFα (20 ng/ml, 48h) or a mixture of allergens (ovalbumin, house dust mite, Alternaria, and Aspergillus extracts) significantly enhanced BDNF secretion and increased TRPC3 expression. TRPC3 knockdown (siRNA or inhibitor Pyr3; 10µM) blunted BDNF secretion, and prevented inflammation effects. Chelation of extracellular Ca2+ (EGTA; 1mM) or intracellular Ca2+ (BAPTA; 5µM) significantly reduced secreted BDNF, as did knockdown of SOCE proteins STIM1 and Orai1 or plasma membrane caveolin-1. Functionally, secreted BDNF had autocrine effects suggested by phosphorylation of high-affinity tropomyosin related kinase TrkB receptor, prevented by chelating extracellular BDNF with chimeric TrkB-Fc. These data emphasize the role of TRPC3 and Ca2+ influx in regulation of BDNF secretion by human ASM and the enhancing effects of inflammation. Given BDNF effects on Ca2+ and cell proliferation, BDNF secretion may contribute to altered airway structure and function in diseases such as asthma.

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Increasing the expression of calcium-permeable TRPC3 and TRPC7 channels enhances constitutive secretion

Cited by 27 publications

References 49 publications

Brain-derived neurotrophic factor in the airways

Brain-derived neurotrophic factor in the airways

TRP channels of intracellular membranes

TRPC3 regulates release of brain-derived neurotrophic factor from human airway smooth muscle

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