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10.1085/jgp.114.5.685 http://scihub22266oqcxt.onion/10.1085/jgp.114.5.685 10532965!2230538!10532965     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Gen+Physiol 1999 ; 114 (5): 685-700 Nephropedia Template TP {{tp|p=10532965|t=1999. A mutation linked with Bartter s syndrome locks Kir 1 1a (ROMK1) channels in a closed state |pdf=|usr=}}{{10532965}} gab.com Text A mutation linked with Bartter s syndrome locks Kir 1 1a (ROMK1) channels in a closed state JO: J Gen Physiol http://www.kidney.de/pget.php?&tw=1&pmid=10532965 #FOAvip Mutations in the inward rectifying renal K(+) channel, Kir 1.1a (ROMK), have been linked with Bartter's syndrome, a familial salt-wasting nephropathy. One disease-causing mutation removes the last 60 amino acids (332-391), implicating a previously unappreciated domain, the extreme COOH terminus, as a necessary functional element. Consistent with this hypothesis, truncated channels (Kir 1.1a 331X) are nonfunctional. In the present study, the roles of this domain were systematically evaluated. When coexpressed with wild-type subunits, Kir 1.1a 331X exerted a negative effect, demonstrating that the mutant channel is synthesized and capable of oligomerization. Plasmalemma localization of Kir 1.1a 331X green fluorescent protein (GFP) fusion construct was indistinguishable from the GFP-wild-type channel, demonstrating that mutant channels are expressed on the oocyte plasma membrane in a nonconductive or locked-closed conformation. Incremental reconstruction of the COOH terminus identified amino acids 332-351 as the critical residues for restoring channel activity and uncovered the nature of the functional defect. Mutant channels that are truncated at the extreme boundary of the required domain (Kir 1.1a 351X) display marked inactivation behavior characterized by frequent occupancy in a long-lived closed state. A critical analysis of the Kir 1.1a 331X dominant negative effect suggests a molecular mechanism underlying the aberrant closed-state stabilization. Coexpression of different doses of mutant with wild-type subunits produced an intermediate dominant negative effect, whereas incorporation of a single mutant into a tetrameric concatemer conferred a complete dominant negative effect. This identifies the extreme COOH terminus as an important subunit interaction domain, controlling the efficiency of oligomerization. Collectively, these observations provide a mechanistic basis for the loss of function in one particular Bartter's-causing mutation and identify a structural element that controls open-state occupancy and determines subunit oligomerization. Based on the overlapping functions of this domain, we speculate that intersubunit interactions within the COOH terminus may regulate the energetics of channel opening. Twit Text FOAVip A mutation linked with Bartter s syndrome locks Kir 1 1a (ROMK1) channels in a closed state ????J Gen Physiol http://www.kidney.de/pget.php?&tw=1&pmid=10532965 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=10532965 #FOAvip English Wikipedia <ref>{{Cite pmid|10532965}}</ref> A mutation linked with Bartter s syndrome locks Kir 1 1a (ROMK1) channels in a closed state #MMPMID10532965 Flagg TP; Tate M; Merot J; Welling PA J Gen Physiol 1999[Nov]; 114 (5): 685-700 PMID10532965show ga Mutations in the inward rectifying renal K(+) channel, Kir 1.1a (ROMK), have been linked with Bartter's syndrome, a familial salt-wasting nephropathy. One disease-causing mutation removes the last 60 amino acids (332-391), implicating a previously unappreciated domain, the extreme COOH terminus, as a necessary functional element. Consistent with this hypothesis, truncated channels (Kir 1.1a 331X) are nonfunctional. In the present study, the roles of this domain were systematically evaluated. When coexpressed with wild-type subunits, Kir 1.1a 331X exerted a negative effect, demonstrating that the mutant channel is synthesized and capable of oligomerization. Plasmalemma localization of Kir 1.1a 331X green fluorescent protein (GFP) fusion construct was indistinguishable from the GFP-wild-type channel, demonstrating that mutant channels are expressed on the oocyte plasma membrane in a nonconductive or locked-closed conformation. Incremental reconstruction of the COOH terminus identified amino acids 332-351 as the critical residues for restoring channel activity and uncovered the nature of the functional defect. Mutant channels that are truncated at the extreme boundary of the required domain (Kir 1.1a 351X) display marked inactivation behavior characterized by frequent occupancy in a long-lived closed state. A critical analysis of the Kir 1.1a 331X dominant negative effect suggests a molecular mechanism underlying the aberrant closed-state stabilization. Coexpression of different doses of mutant with wild-type subunits produced an intermediate dominant negative effect, whereas incorporation of a single mutant into a tetrameric concatemer conferred a complete dominant negative effect. This identifies the extreme COOH terminus as an important subunit interaction domain, controlling the efficiency of oligomerization. Collectively, these observations provide a mechanistic basis for the loss of function in one particular Bartter's-causing mutation and identify a structural element that controls open-state occupancy and determines subunit oligomerization. Based on the overlapping functions of this domain, we speculate that intersubunit interactions within the COOH terminus may regulate the energetics of channel opening. |*Frameshift Mutation[MESH] |*Potassium Channels, Inwardly Rectifying[MESH] |Animals[MESH] |Bartter Syndrome/*genetics/physiopathology[MESH] |Cell Membrane/chemistry/physiology[MESH] |Electrophysiology[MESH] |Female[MESH] |Gene Deletion[MESH] |Gene Expression/physiology[MESH] |Genes, Reporter[MESH] |Green Fluorescent Proteins[MESH] |Humans[MESH] |Indicators and Reagents[MESH] |Ion Channel Gating/*genetics[MESH] |Luminescent Proteins/genetics[MESH] |Membrane Potentials/genetics[MESH] |Microscopy, Confocal[MESH] |Molecular Sequence Data[MESH] |Mutagenesis/physiology[MESH] |Oocytes/physiology[MESH] |Potassium Channels/*genetics/metabolism[MESH] |Sequence Homology, Amino Acid[MESH]A mutation linked with Bartter s syndrome locks Kir 1 1a (ROMK1) chann(epmc).pdf DeepDyve Pubget Overpricing