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10.1074/jbc.M113.540948 http://scihub22266oqcxt.onion/10.1074/jbc.M113.540948 24526686!3975042!24526686     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       J+Biol+Chem 2014 ; 289 (14): 9983-97 Nephropedia Template TP {{tp|p=24526686|t=2014. Annexin A2 mediates apical trafficking of renal Na(+)-K(+)-2Cl(-) cotransporter |pdf=|usr=}}{{24526686}} gab.com Text Annexin A2 mediates apical trafficking of renal Na(+)-K(+)-2Cl(-) cotransporter JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=24526686 #FOAvip The furosemide-sensitive Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) is responsible for urine concentration and helps maintain systemic salt homeostasis. Its activity depends on trafficking to, and insertion into, the apical membrane, as well as on phosphorylation of conserved N-terminal serine and threonine residues. Vasopressin (AVP) signaling via PKA and other kinases activates NKCC2. Association of NKCC2 with lipid rafts facilitates its AVP-induced apical translocation and activation at the surface. Lipid raft microdomains typically serve as platforms for membrane proteins to facilitate their interactions with other proteins, but little is known about partners that interact with NKCC2. Yeast two-hybrid screening identified an interaction between NKCC2 and the cytosolic protein, annexin A2 (AnxA2). Annexins mediate lipid raft-dependent trafficking of transmembrane proteins, including the AVP-regulated water channel, aquaporin 2. Here, we demonstrate that AnxA2, which binds to phospholipids in a Ca(2+)-dependent manner and may organize microdomains, is codistributed with NKCC2 to promote its apical translocation in response to AVP stimulation and low chloride hypotonic stress. NKCC2 and AnxA2 interact in a phosphorylation-dependent manner. Phosphomimetic AnxA2 carrying a mutant phosphoacceptor (AnxA2-Y24D-GFP) enhanced surface expression and raft association of NKCC2 by 5-fold upon low chloride hypotonic stimulation, whereas AnxA2-Y24A-GFP and PKC-dependent AnxA2-S26D-GFP did not. As the AnxA2 effect involved only nonphosphorylated NKCC2, it appears to affect NKCC2 trafficking. Overexpression or knockdown experiments further supported the role of AnxA2 in the apical translocation and surface expression of NKCC2. In summary, this study identifies AnxA2 as a lipid raft-associated trafficking factor for NKCC2 and provides mechanistic insight into the regulation of this essential cotransporter. Twit Text FOAVip Annexin A2 mediates apical trafficking of renal Na(+)-K(+)-2Cl(-) cotransporter ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=24526686 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24526686 #FOAvip English Wikipedia <ref>{{Cite pmid|24526686}}</ref> Annexin A2 mediates apical trafficking of renal Na(+)-K(+)-2Cl(-) cotransporter #MMPMID24526686 Dathe C; Daigeler AL; Seifert W; Jankowski V; Mrowka R; Kalis R; Wanker E; Mutig K; Bachmann S; Paliege A J Biol Chem 2014[Apr]; 289 (14): 9983-97 PMID24526686show ga The furosemide-sensitive Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) is responsible for urine concentration and helps maintain systemic salt homeostasis. Its activity depends on trafficking to, and insertion into, the apical membrane, as well as on phosphorylation of conserved N-terminal serine and threonine residues. Vasopressin (AVP) signaling via PKA and other kinases activates NKCC2. Association of NKCC2 with lipid rafts facilitates its AVP-induced apical translocation and activation at the surface. Lipid raft microdomains typically serve as platforms for membrane proteins to facilitate their interactions with other proteins, but little is known about partners that interact with NKCC2. Yeast two-hybrid screening identified an interaction between NKCC2 and the cytosolic protein, annexin A2 (AnxA2). Annexins mediate lipid raft-dependent trafficking of transmembrane proteins, including the AVP-regulated water channel, aquaporin 2. Here, we demonstrate that AnxA2, which binds to phospholipids in a Ca(2+)-dependent manner and may organize microdomains, is codistributed with NKCC2 to promote its apical translocation in response to AVP stimulation and low chloride hypotonic stress. NKCC2 and AnxA2 interact in a phosphorylation-dependent manner. Phosphomimetic AnxA2 carrying a mutant phosphoacceptor (AnxA2-Y24D-GFP) enhanced surface expression and raft association of NKCC2 by 5-fold upon low chloride hypotonic stimulation, whereas AnxA2-Y24A-GFP and PKC-dependent AnxA2-S26D-GFP did not. As the AnxA2 effect involved only nonphosphorylated NKCC2, it appears to affect NKCC2 trafficking. Overexpression or knockdown experiments further supported the role of AnxA2 in the apical translocation and surface expression of NKCC2. In summary, this study identifies AnxA2 as a lipid raft-associated trafficking factor for NKCC2 and provides mechanistic insight into the regulation of this essential cotransporter. |Amino Acid Substitution[MESH] |Animals[MESH] |Annexin A2/genetics/*metabolism[MESH] |Antidiuretic Agents/pharmacology[MESH] |HEK293 Cells[MESH] |Humans[MESH] |Macaca mulatta[MESH] |Male[MESH] |Membrane Microdomains/genetics/*metabolism[MESH] |Mutation, Missense[MESH] |Phosphorylation/drug effects/genetics[MESH] |Protein Transport/drug effects/genetics[MESH] |Rats[MESH] |Rats, Sprague-Dawley[MESH] |Solute Carrier Family 12, Member 1/genetics/*metabolism[MESH]Annexin A2 mediates apical trafficking of renal Na(+)-K(+)-2Cl(-) cotr(epmc).pdf DeepDyve Pubget Overpricing