An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells
Publication Date
January 26, 2018
Authors
Katharina Schrade, Jessica Tröger, Adeeb Eldahshan, Kerstin Zühlke, et al
Volume
13
Issue
1
Pages
e0191423
DOI
https://dx.plos.org/10.1371/journal.pone.0191423
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0191423
Scopus
85041056211
Mendeley
http://www.mendeley.com/research/akaplbcrhoa-interaction-inhibitor-promotes-translocation-aquaporin2-plasma-membrane-renal-collecting
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{"title"=>"An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells", "type"=>"journal", "authors"=>[{"first_name"=>"Katharina", "last_name"=>"Schrade"}, {"first_name"=>"Jessica", "last_name"=>"Tröger"}, {"first_name"=>"Adeeb", "last_name"=>"Eldahshan"}, {"first_name"=>"Kerstin", "last_name"=>"Zühlke"}, {"first_name"=>"Kamal R.", "last_name"=>"Abdul Azeez"}, {"first_name"=>"Jonathan M", "last_name"=>"Elkins"}, {"first_name"=>"Martin", "last_name"=>"Neuenschwander"}, {"first_name"=>"Andreas", "last_name"=>"Oder"}, {"first_name"=>"Mohamed", "last_name"=>"Elkewedi"}, {"first_name"=>"Sarah", "last_name"=>"Jaksch"}, {"first_name"=>"Karsten", "last_name"=>"Andrae"}, {"first_name"=>"Jinliang", "last_name"=>"Li"}, {"first_name"=>"Joao", "last_name"=>"Fernandes"}, {"first_name"=>"Paul Markus", "last_name"=>"Müller"}, {"first_name"=>"Stephan", "last_name"=>"Grunwald"}, {"first_name"=>"Stephen F", "last_name"=>"Marino"}, {"first_name"=>"Tanja", "last_name"=>"Vukićević"}, {"first_name"=>"Jenny", "last_name"=>"Eichhorst"}, {"first_name"=>"Burkhard", "last_name"=>"Wiesner"}, {"first_name"=>"Marcus", "last_name"=>"Weber"}, {"first_name"=>"Michael", "last_name"=>"Kapiloff"}, {"first_name"=>"Oliver", "last_name"=>"Rocks"}, {"first_name"=>"Oliver", "last_name"=>"Daumke"}, {"first_name"=>"Thomas", "last_name"=>"Wieland"}, {"first_name"=>"Stefan", "last_name"=>"Knapp"}, {"first_name"=>"Jens Peter", "last_name"=>"von Kries"}, {"first_name"=>"Enno", "last_name"=>"Klussmann"}], "year"=>2018, "source"=>"PloS ONE", "identifiers"=>{"issn"=>"1932-6203", "scopus"=>"2-s2.0-85041056211", "sgr"=>"85041056211", "pui"=>"620329770", "isbn"=>"1111111111", "pmid"=>"29373579", "doi"=>"10.1371/journal.pone.0191423"}, "id"=>"f191288b-8723-3bcd-b883-c3ebae87cd22", "abstract"=>"Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking.", "link"=>"http://www.mendeley.com/research/akaplbcrhoa-interaction-inhibitor-promotes-translocation-aquaporin2-plasma-membrane-renal-collecting", "reader_count"=>6, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Ph. D. Student"=>1, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Ph. D. Student"=>1, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

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