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10.1016/j.molmet.2016.05.015 http://scihub22266oqcxt.onion/10.1016/j.molmet.2016.05.015 C5021679!5021679 !27656403     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 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\27656403 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Mol+Metab 2016 ; 5 (8 ): 656-668 Nephropedia Template TP {{tp|p=27656403 |t=2016. The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512 |pdf=|usr=}}{{27656403 }} gab.com Text The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512 JO: Mol Metab http://www.kidney.de/pget.php?&tw=1&pmid=27656403 #FOAvip OBJECTIVE: Insulin release from pancreatic islet ? cells should be tightly controlled to avoid hypoglycemia and insulin resistance. The cortical actin cytoskeleton is a gate for regulated exocytosis of insulin secretory granules (SGs) by restricting their mobility and access to the plasma membrane. Prior studies suggest that SGs interact with F-actin through their transmembrane cargo islet cell autoantigen 512 (Ica512) (also known as islet antigen 2/Ptprn). Here we investigated how Ica512 modulates SG trafficking and exocytosis. METHODS: Transcriptomic changes in Ica512 (-/-) mouse islets were analyzed. Imaging as well as biophysical and biochemical methods were used to validate if and how the Ica512-regulated gene villin modulates insulin secretion in mouse islets and insulinoma cells. RESULTS: The F-actin modifier villin was consistently downregulated in Ica512 (-/-) mouse islets and in Ica512-depleted insulinoma cells. Villin was enriched at the cell cortex of ? cells and dispersed villin (-/-) islet cells were less round and less deformable. Basal mobility of SGs in villin-depleted cells was enhanced. Moreover, in cells depleted either of villin or Ica512 F-actin cages restraining cortical SGs were enlarged, basal secretion was increased while glucose-stimulated insulin release was blunted. The latter changes were reverted by overexpressing villin in Ica512-depleted cells, but not vice versa. CONCLUSION: Our findings show that villin controls the size of the F-actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion. Twit Text FOAVip The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512 ????Mol Metab http://www.kidney.de/pget.php?&tw=1&pmid=27656403 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27656403 #FOAvip English Wikipedia <ref>{{Cite pmid|27656403 }}</ref> The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512 #MMPMID27656403 Mziaut H ; Mulligan B ; Hoboth P ; Otto O ; Ivanova A ; Herbig M ; Schumann D ; Hildebrandt T ; Dehghany J ; Sönmez A ; Münster C ; Meyer-Hermann M ; Guck J ; Kalaidzidis Y ; Solimena M Mol Metab 2016[Aug]; 5 (8 ): 656-668 PMID27656403 show ga OBJECTIVE: Insulin release from pancreatic islet ? cells should be tightly controlled to avoid hypoglycemia and insulin resistance. The cortical actin cytoskeleton is a gate for regulated exocytosis of insulin secretory granules (SGs) by restricting their mobility and access to the plasma membrane. Prior studies suggest that SGs interact with F-actin through their transmembrane cargo islet cell autoantigen 512 (Ica512) (also known as islet antigen 2/Ptprn). Here we investigated how Ica512 modulates SG trafficking and exocytosis. METHODS: Transcriptomic changes in Ica512 (-/-) mouse islets were analyzed. Imaging as well as biophysical and biochemical methods were used to validate if and how the Ica512-regulated gene villin modulates insulin secretion in mouse islets and insulinoma cells. RESULTS: The F-actin modifier villin was consistently downregulated in Ica512 (-/-) mouse islets and in Ica512-depleted insulinoma cells. Villin was enriched at the cell cortex of ? cells and dispersed villin (-/-) islet cells were less round and less deformable. Basal mobility of SGs in villin-depleted cells was enhanced. Moreover, in cells depleted either of villin or Ica512 F-actin cages restraining cortical SGs were enlarged, basal secretion was increased while glucose-stimulated insulin release was blunted. The latter changes were reverted by overexpressing villin in Ica512-depleted cells, but not vice versa. CONCLUSION: Our findings show that villin controls the size of the F-actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion. äThe F-actin modifier villin regulates insulin granule dynamics and exo(epmc).pdf DeepDyve Pubget Overpricing