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10.1074/jbc.RA117.001547 http://scihub22266oqcxt.onion/10.1074/jbc.RA117.001547 C5971468!5971468!29615494     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29615494.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Biol+Chem 2018 ; 293 (21): 8217-29 Nephropedia Template TP {{tp|p=29615494|t=2018. Small molecules that inhibit the late stage of Munc13-4?dependent secretory granule exocytosis in mast cells |pdf=|usr=}}{{29615494}} gab.com Text Small molecules that inhibit the late stage of Munc13-4 dependent secretory granule exocytosis in mast cells JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=29615494 #FOAvip Ca2+-dependent secretory granule fusion with the plasma membrane is the final step for the exocytic release of inflammatory mediators, neuropeptides, and peptide hormones. Secretory cells use a similar protein machinery at late steps in the regulated secretory pathway, employing protein isoforms from the Rab, Sec1/Munc18, Munc13/CAPS, SNARE, and synaptotagmin protein families. However, no small-molecule inhibitors of secretory granule exocytosis that target these proteins are currently available but could have clinical utility. Here we utilized a high-throughput screen of a 25,000-compound library that identified 129 small-molecule inhibitors of Ca2+-triggered secretory granule exocytosis in RBL-2H3 mast cells. These inhibitors broadly fell into six different chemical classes, and follow-up permeable cell and liposome fusion assays identified the target for one class of these inhibitors. A family of 2-aminobenzothiazoles (termed benzothiazole exocytosis inhibitors or bexins) was found to inhibit mast cell secretory granule fusion by acting on a Ca2+-dependent, C2 domain?containing priming factor, Munc13-4. Our findings further indicated that bexins interfere with Munc13-4?membrane interactions and thereby inhibit Munc13-4?dependent membrane fusion. We conclude that bexins represent a class of specific secretory pathway inhibitors with potential as therapeutic agents. Twit Text FOAVip Small molecules that inhibit the late stage of Munc13-4 dependent secretory granule exocytosis in mast cells ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=29615494 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29615494 #FOAvip English Wikipedia <ref>{{Cite pmid|29615494}}</ref> Small molecules that inhibit the late stage of Munc13-4?dependent secretory granule exocytosis in mast cells #MMPMID29615494 Bruinsma S; James DJ; Quintana Serrano M; Esquibel J; Woo SS; Kielar-Grevstad E; Crummy E; Qurashi R; Kowalchyk JA; Martin TFJ J Biol Chem 2018[May]; 293 (21): 8217-29 PMID29615494show ga Ca2+-dependent secretory granule fusion with the plasma membrane is the final step for the exocytic release of inflammatory mediators, neuropeptides, and peptide hormones. Secretory cells use a similar protein machinery at late steps in the regulated secretory pathway, employing protein isoforms from the Rab, Sec1/Munc18, Munc13/CAPS, SNARE, and synaptotagmin protein families. However, no small-molecule inhibitors of secretory granule exocytosis that target these proteins are currently available but could have clinical utility. Here we utilized a high-throughput screen of a 25,000-compound library that identified 129 small-molecule inhibitors of Ca2+-triggered secretory granule exocytosis in RBL-2H3 mast cells. These inhibitors broadly fell into six different chemical classes, and follow-up permeable cell and liposome fusion assays identified the target for one class of these inhibitors. A family of 2-aminobenzothiazoles (termed benzothiazole exocytosis inhibitors or bexins) was found to inhibit mast cell secretory granule fusion by acting on a Ca2+-dependent, C2 domain?containing priming factor, Munc13-4. Our findings further indicated that bexins interfere with Munc13-4?membrane interactions and thereby inhibit Munc13-4?dependent membrane fusion. We conclude that bexins represent a class of specific secretory pathway inhibitors with potential as therapeutic agents. äSmall molecules that inhibit the late stage of Munc13-4?dependent secr(epmc).pdf DeepDyve Pubget Overpricing