Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.

Guanylate-binding proteins (GBPs) belong to the dynamin family of large GTPases and represent the major IFN-γ-induced proteins. Here we systematically investigated the mechanisms regulating the subcellular localization of GBPs. Three GBPs (GBP-1, GBP-2 and GBP-5) carry a C-terminal CaaX-prenylation...

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Autores principales:	Nathalie Britzen-Laurent, Michael Bauer, Valeria Berton, Nicole Fischer, Adrian Syguda, Simone Reipschläger, Elisabeth Naschberger, Christian Herrmann, Michael Stürzl
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c0564ff453b4b27a2a536fbf6ecced8
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spelling	oai:doaj.org-article:0c0564ff453b4b27a2a536fbf6ecced82021-11-18T07:02:00ZIntracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.1932-620310.1371/journal.pone.0014246https://doaj.org/article/0c0564ff453b4b27a2a536fbf6ecced82010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21151871/?tool=EBIhttps://doaj.org/toc/1932-6203Guanylate-binding proteins (GBPs) belong to the dynamin family of large GTPases and represent the major IFN-γ-induced proteins. Here we systematically investigated the mechanisms regulating the subcellular localization of GBPs. Three GBPs (GBP-1, GBP-2 and GBP-5) carry a C-terminal CaaX-prenylation signal, which is typical for small GTPases of the Ras family, and increases the membrane affinity of proteins. In this study, we demonstrated that GBP-1, GBP-2 and GBP-5 are prenylated in vivo and that prenylation is required for the membrane association of GBP-1, GBP-2 and GBP-5. Using co-immunoprecipitation, yeast-two-hybrid analysis and fluorescence complementation assays, we showed for the first time that GBPs are able to homodimerize in vivo and that the membrane association of GBPs is regulated by dimerization similarly to dynamin. Interestingly, GBPs could also heterodimerize. This resulted in hierarchical positioning effects on the intracellular localization of the proteins. Specifically, GBP-1 recruited GBP-5 and GBP-2 into its own cellular compartment and GBP-5 repositioned GBP-2. In addition, GBP-1, GBP-2 and GBP-5 were able to redirect non-prenylated GBPs to their compartment in a prenylation-dependent manner. Overall, these findings prove in vivo the ability of GBPs to dimerize, indicate that heterodimerization regulates sub-cellular localization of GBPs and underscore putative membrane-associated functions of this family of proteins.Nathalie Britzen-LaurentMichael BauerValeria BertonNicole FischerAdrian SygudaSimone ReipschlägerElisabeth NaschbergerChristian HerrmannMichael StürzlPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e14246 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nathalie Britzen-Laurent Michael Bauer Valeria Berton Nicole Fischer Adrian Syguda Simone Reipschläger Elisabeth Naschberger Christian Herrmann Michael Stürzl Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.
description	Guanylate-binding proteins (GBPs) belong to the dynamin family of large GTPases and represent the major IFN-γ-induced proteins. Here we systematically investigated the mechanisms regulating the subcellular localization of GBPs. Three GBPs (GBP-1, GBP-2 and GBP-5) carry a C-terminal CaaX-prenylation signal, which is typical for small GTPases of the Ras family, and increases the membrane affinity of proteins. In this study, we demonstrated that GBP-1, GBP-2 and GBP-5 are prenylated in vivo and that prenylation is required for the membrane association of GBP-1, GBP-2 and GBP-5. Using co-immunoprecipitation, yeast-two-hybrid analysis and fluorescence complementation assays, we showed for the first time that GBPs are able to homodimerize in vivo and that the membrane association of GBPs is regulated by dimerization similarly to dynamin. Interestingly, GBPs could also heterodimerize. This resulted in hierarchical positioning effects on the intracellular localization of the proteins. Specifically, GBP-1 recruited GBP-5 and GBP-2 into its own cellular compartment and GBP-5 repositioned GBP-2. In addition, GBP-1, GBP-2 and GBP-5 were able to redirect non-prenylated GBPs to their compartment in a prenylation-dependent manner. Overall, these findings prove in vivo the ability of GBPs to dimerize, indicate that heterodimerization regulates sub-cellular localization of GBPs and underscore putative membrane-associated functions of this family of proteins.
format	article
author	Nathalie Britzen-Laurent Michael Bauer Valeria Berton Nicole Fischer Adrian Syguda Simone Reipschläger Elisabeth Naschberger Christian Herrmann Michael Stürzl
author_facet	Nathalie Britzen-Laurent Michael Bauer Valeria Berton Nicole Fischer Adrian Syguda Simone Reipschläger Elisabeth Naschberger Christian Herrmann Michael Stürzl
author_sort	Nathalie Britzen-Laurent
title	Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.
title_short	Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.
title_full	Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.
title_fullStr	Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.
title_full_unstemmed	Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.
title_sort	intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/0c0564ff453b4b27a2a536fbf6ecced8
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Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.

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