Endogenous Modulators of TRP Channels

2013 ◽  
Vol 13 (3) ◽  
pp. 398-407 ◽  
Author(s):  
Enza Palazzo ◽  
Francesco Rossi ◽  
Vito de Novellis ◽  
Sabatino Maione
2020 ◽  
Vol 21 (12) ◽  
pp. 4323
Author(s):  
Kristyna Bousova ◽  
Ivan Barvik ◽  
Petr Herman ◽  
Kateřina Hofbauerová ◽  
Lenka Monincova ◽  
...  

Molecular determinants of the binding of various endogenous modulators to transient receptor potential (TRP) channels are crucial for the understanding of necessary cellular pathways, as well as new paths for rational drug designs. The aim of this study was to characterise interactions between the TRP cation channel subfamily melastatin member 4 (TRPM4) and endogenous intracellular modulators—calcium-binding proteins (calmodulin (CaM) and S100A1) and phosphatidylinositol 4, 5-bisphosphate (PIP2). We have found binding epitopes at the N- and C-termini of TRPM4 shared by CaM, S100A1 and PIP2. The binding affinities of short peptides representing the binding epitopes of N- and C-termini were measured by means of fluorescence anisotropy (FA). The importance of representative basic amino acids and their combinations from both peptides for the binding of endogenous TRPM4 modulators was proved using point alanine-scanning mutagenesis. In silico protein–protein docking of both peptides to CaM and S100A1 and extensive molecular dynamics (MD) simulations enabled the description of key stabilising interactions at the atomic level. Recently solved cryo-Electron Microscopy (EM) structures made it possible to put our findings into the context of the entire TRPM4 channel and to deduce how the binding of these endogenous modulators could allosterically affect the gating of TRPM4. Moreover, both identified binding epitopes seem to be ideally positioned to mediate the involvement of TRPM4 in higher-order hetero-multimeric complexes with important physiological functions.


2013 ◽  
Vol 13 (3) ◽  
pp. 283-294 ◽  
Author(s):  
Hiroyuki Watanabe ◽  
Kenji Iino ◽  
Takayoshi Ohba ◽  
Hiroshi Ito

2013 ◽  
Vol 11 (4) ◽  
pp. 480-489 ◽  
Author(s):  
Isaac Jardin ◽  
Natalia Dionisio ◽  
Jose Lopez ◽  
Gines Salido ◽  
Juan Rosado
Keyword(s):  

2014 ◽  
Vol 15 (9) ◽  
pp. 16430-16457 ◽  
Author(s):  
Seung-In Choi ◽  
Sungjae Yoo ◽  
Ji Lim ◽  
Sun Hwang

2021 ◽  
pp. 174185
Author(s):  
Amanda Spring de Almeida ◽  
Laura de Barros Bernardes ◽  
Gabriela Trevisan
Keyword(s):  

Author(s):  
Saied Froghi ◽  
Charlotte R. Grant ◽  
Radhika Tandon ◽  
Alberto Quaglia ◽  
Brian Davidson ◽  
...  

AbstractCalcium is the most abundant mineral in the human body and is central to many physiological processes, including immune system activation and maintenance. Studies continue to reveal the intricacies of calcium signalling within the immune system. Perhaps the most well-understood mechanism of calcium influx into cells is store-operated calcium entry (SOCE), which occurs via calcium release-activated channels (CRACs). SOCE is central to the activation of immune system cells; however, more recent studies have demonstrated the crucial role of other calcium channels, including transient receptor potential (TRP) channels. In this review, we describe the expression and function of TRP channels within the immune system and outline associations with murine models of disease and human conditions. Therefore, highlighting the importance of TRP channels in disease and reviewing potential. The TRP channel family is significant, and its members have a continually growing number of cellular processes. Within the immune system, TRP channels are involved in a diverse range of functions including T and B cell receptor signalling and activation, antigen presentation by dendritic cells, neutrophil and macrophage bactericidal activity, and mast cell degranulation. Not surprisingly, these channels have been linked to many pathological conditions such as inflammatory bowel disease, chronic fatigue syndrome and myalgic encephalomyelitis, atherosclerosis, hypertension and atopy.


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