SAP97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its PDZ2 and I3 domains.

Previous studies have determined that the type-1 PDZ sequence at the extreme carboxy-terminus of the ß1-adrenergic receptor (ß1-AR) binds SAP97 and AKAP79 to organize a scaffold involved in trafficking of the ß1-AR. In this study we focused on characterizing the domains in SAP97 that were involved i...

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Autores principales:	Mohammed M Nooh, Anjaparavanda P Naren, Sung-Jin Kim, Yang K Xiang, Suleiman W Bahouth
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9bb5220e3f234ac1af80491637a33972
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spelling	oai:doaj.org-article:9bb5220e3f234ac1af80491637a339722021-11-18T07:45:30ZSAP97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its PDZ2 and I3 domains.1932-620310.1371/journal.pone.0063379https://doaj.org/article/9bb5220e3f234ac1af80491637a339722013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23696820/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Previous studies have determined that the type-1 PDZ sequence at the extreme carboxy-terminus of the ß1-adrenergic receptor (ß1-AR) binds SAP97 and AKAP79 to organize a scaffold involved in trafficking of the ß1-AR. In this study we focused on characterizing the domains in SAP97 that were involved in recycling and resensitization of the ß1-AR in HEK-293 cells. Using a SAP97 knockdown and rescue strategy, we determined that PDZ-deletion mutants of SAP97 containing PDZ2 rescued the recycling and resensitization of the ß1-AR. Among the three PDZs of SAP97, PDZ2 displayed the highest affinity in binding to the ß1-AR. Expression of isolated PDZ2, but not the other PDZs, inhibited the recycling of the ß1-AR by destabilizing the macromolecular complex involved in trafficking and functional resensitization of the ß1-AR. In addition to its PDZs, SAP97 contains other protein interacting domains, such as the I3 sequence in the SRC homology-3 (SH3) domain, which binds to AKAP79. Deletion of I3 from SAP97 (ΔI3-SAP97) did not affect the binding of SAP97 to the ß1-AR. However, ΔI3-SAP97 could not rescue the recycling of the ß1-AR because it failed to incorporate AKAP79/PKA into the SAP97-ß1-AR complex. Therefore, bipartite binding of SAP97 to the ß1-AR and to AKAP79 is necessary for SAP97-mediated effects on recycling, externalization and functional resensitization of the ß1-AR. These data establish a prominent role for PDZ2 and I3 domains of SAP97 in organizing the ß1-adrenergic receptosome involved in connecting the ß1-AR to trafficking and signaling networks.Mohammed M NoohAnjaparavanda P NarenSung-Jin KimYang K XiangSuleiman W BahouthPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e63379 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohammed M Nooh Anjaparavanda P Naren Sung-Jin Kim Yang K Xiang Suleiman W Bahouth SAP97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its PDZ2 and I3 domains.
description	Previous studies have determined that the type-1 PDZ sequence at the extreme carboxy-terminus of the ß1-adrenergic receptor (ß1-AR) binds SAP97 and AKAP79 to organize a scaffold involved in trafficking of the ß1-AR. In this study we focused on characterizing the domains in SAP97 that were involved in recycling and resensitization of the ß1-AR in HEK-293 cells. Using a SAP97 knockdown and rescue strategy, we determined that PDZ-deletion mutants of SAP97 containing PDZ2 rescued the recycling and resensitization of the ß1-AR. Among the three PDZs of SAP97, PDZ2 displayed the highest affinity in binding to the ß1-AR. Expression of isolated PDZ2, but not the other PDZs, inhibited the recycling of the ß1-AR by destabilizing the macromolecular complex involved in trafficking and functional resensitization of the ß1-AR. In addition to its PDZs, SAP97 contains other protein interacting domains, such as the I3 sequence in the SRC homology-3 (SH3) domain, which binds to AKAP79. Deletion of I3 from SAP97 (ΔI3-SAP97) did not affect the binding of SAP97 to the ß1-AR. However, ΔI3-SAP97 could not rescue the recycling of the ß1-AR because it failed to incorporate AKAP79/PKA into the SAP97-ß1-AR complex. Therefore, bipartite binding of SAP97 to the ß1-AR and to AKAP79 is necessary for SAP97-mediated effects on recycling, externalization and functional resensitization of the ß1-AR. These data establish a prominent role for PDZ2 and I3 domains of SAP97 in organizing the ß1-adrenergic receptosome involved in connecting the ß1-AR to trafficking and signaling networks.
format	article
author	Mohammed M Nooh Anjaparavanda P Naren Sung-Jin Kim Yang K Xiang Suleiman W Bahouth
author_facet	Mohammed M Nooh Anjaparavanda P Naren Sung-Jin Kim Yang K Xiang Suleiman W Bahouth
author_sort	Mohammed M Nooh
title	SAP97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its PDZ2 and I3 domains.
title_short	SAP97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its PDZ2 and I3 domains.
title_full	SAP97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its PDZ2 and I3 domains.
title_fullStr	SAP97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its PDZ2 and I3 domains.
title_full_unstemmed	SAP97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its PDZ2 and I3 domains.
title_sort	sap97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its pdz2 and i3 domains.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9bb5220e3f234ac1af80491637a33972
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SAP97 controls the trafficking and resensitization of the beta-1-adrenergic receptor through its PDZ2 and I3 domains.

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