Proinflammatory Mediators Modulate the Heat-Activated Ion Channel TRPV1 via the Scaffolding Protein AKAP79/150

Zhang, Xuming; Lin, L.Y.; McNaughton, Peter A.

doi:10.1016/j.neuron.2008.05.015

Cited by 240 publications

(311 citation statements)

References 63 publications

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“…The first hypothesis, discussed previously, is supported by several reports on PKA-dependent NOS phosphorylation and activation (21,32,33). The second explanation, pointing to an effect on calcium channels, would be in agreement with PKAdependent phosphorylation of calcium-permeable channels reported for ECs and other cell types (34)(35)(36).…”

Section: Discussionsupporting

confidence: 83%

Multiple Roles of Protein Kinase A in Arachidonic Acid–Mediated Ca2+ Entry and Tumor-Derived Human Endothelial Cell Migration

Fiorio

Genova

Pupo

et al. 2010

Molecular Cancer Research

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We recently showed that arachidonic acid (AA) triggers calcium signals in endothelial cells derived from human breast carcinoma (B-TEC). In particular, AA-dependent Ca 2+ entry is involved in the early steps of tumor angiogenesis in vitro. Here, we investigated the multiple roles of the nitric oxide (NO) and cyclic AMP/protein kinase A (PKA) pathways in AA-mediated Ca 2+ signaling in the same cells. B-TEC stimulation with 5 μmol/L AA resulted in endothelial NO synthase (NOS) phosphorylation at Ser 1177 , and NO release was measured with the fluorescent NO-sensitive probe DAR4M-AM. PKA inhibition by the use of the membrane-permeable PKA inhibitory peptide myristoylated PKI 14-22 completely prevented both AA-and NOinduced calcium entry and abolished B-TEC migration promoted by AA. AA-dependent calcium entry and cell migration were significantly affected by both the NOS inhibitor N G -nitro-L-arginine methyl ester and the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, suggesting that NO release is functionally involved in the signaling dependent on AA. Moreover, pretreatment with carboxyamidotriazole, an antiangiogenic compound that interferes with agonist-activated calcium entry, prevented AA-dependent B-TEC motility. Interestingly, even in the absence of AA, enhancement of the cyclic AMP/PKA pathway with the adenylyl cyclase activator forskolin evoked a calcium entry dependent on NOS recruitment and NO release. The functional relevance of AA-induced calcium entry could be restricted to tumor-derived endothelial cells (EC) because AA evoked a smaller calcium entry in normal human microvascular ECs compared with B-TECs, and even more importantly, it was unable to promote cell motility in wound healing assay. This evidence opens an intriguing opportunity for differential pharmacologic treatment between normal and tumor-derived human ECs.

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Section: Discussionsupporting

confidence: 83%

Multiple Roles of Protein Kinase A in Arachidonic Acid–Mediated Ca2+ Entry and Tumor-Derived Human Endothelial Cell Migration

Fiorio

Genova

Pupo

et al. 2010

Molecular Cancer Research

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“…A second option is that these amino acids may determine TRPM6 function by providing docking sites for physiological ligands, signaling proteins, or by interacting with scaffolding proteins that have been shown to be essential for modulating the gating properties of other TRP members. 35 As hypomagnesemia can be multifactorial and multigenic, studies of isolated monogenic disorders represent a valuable tool to disclose the role of a single gene for Mg 2 þ metabolism. Naturally occurring missense mutations inform about key amino acids involved in the function of such proteins.…”

Section: Discussionmentioning

confidence: 99%

New TRPM6 missense mutations linked to hypomagnesemia with secondary hypocalcemia

et al. 2013

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Despite recent progress in our understanding of renal magnesium (Mg 2 þ ) handling, the molecular mechanisms accounting for transepithelial Mg 2 þ transport are still poorly understood. Mutations in the TRPM6 gene, encoding the epithelial Mg 2 þ channel TRPM6 (transient receptor potential melastatin 6), have been proven to be the molecular cause of hypomagnesemia with secondary hypocalcemia (HSH; OMIM 602014). HSH manifests in the newborn period being characterized by very low serum Mg 2 þ levels (o0.4 mmol/l) accompanied by low serum calcium (Ca 2 þ ) concentrations. A proportion of previously described TRPM6 mutations lead to a truncated TRPM6 protein resulting in a complete loss-of-function of the ion channel. In addition, five-point mutations have been previously described. The aim of this study was to complement the current clinical picture by adding the molecular data from five new missense mutations found in five patients with HSH. To this end, patch-clamp analysis and cell surface measurements were performed to assess the effect of the various mutations on TRPM6 channel function. All mutant channels, expressed in HEK293 cells, showed loss-of-function, whereas no severe trafficking impairment to the plasma membrane surface was observed. We conclude that the new TRPM6 missense mutations lead to dysregulated intestinal/renal Mg 2 þ (re)absorption as a consequence of loss of TRPM6 channel function.

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“…Areas of photoactivation of opto- 1 AR ranged from 3 to 12 µm 2 . To prevent Ca 2+ release from intracellular stores via IP 3 receptors, The interactions between AKAP150 and TRPV4 channels are dynamic Although TRPV4 and AKAP79 (the human orthologue of AKAP150) have been shown to coimmunoprecipitate (Zhang et al, 2008), there is no direct evidence indicating that they interact in cells. This is important because in living cells the number and strength of AKAP150-TRPV4 interactions could be under the control of multiple physiological processes.…”

Section: Trpv4 Channels Oppose Angii-induced Vasoconstrictionmentioning

confidence: 99%

Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle

Mercado¹,

Baylie²,

Navedo³

et al. 2014

J Cell Biol

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Proinflammatory Mediators Modulate the Heat-Activated Ion Channel TRPV1 via the Scaffolding Protein AKAP79/150

Cited by 240 publications

References 63 publications

Multiple Roles of Protein Kinase A in Arachidonic Acid–Mediated Ca2+ Entry and Tumor-Derived Human Endothelial Cell Migration

Multiple Roles of Protein Kinase A in Arachidonic Acid–Mediated Ca2+ Entry and Tumor-Derived Human Endothelial Cell Migration

New TRPM6 missense mutations linked to hypomagnesemia with secondary hypocalcemia

Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle

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