title: γ2 and γ1AP-1 complexes: Different essential functions and regulatory mechanisms in clathrin-dependent protein sorting.
abstract: γ2 adaptin is homologous to γ1, but is only expressed in vertebrates while γ1 is found in all eukaryotes. We know little about γ2 functions and their relation to γ1. γ1 is an adaptin of the heterotetrameric AP-1 complexes, which sort proteins in and do form clathrin-coated transport vesicles and they also regulate maturation of early endosomes. γ1 knockout mice develop only to blastocysts and thus γ2 does not compensate γ1-deficiency in development. γ2 has not been classified as a clathrin-coated vesicle adaptor protein in proteome analyses and functions for monomeric γ2 in endosomal protein sorting have been proposed, but adaptin interaction studies suggested formation of heterotetrameric AP-1/γ2 complexes. We detected γ2 at the trans-Golgi network, on peripheral vesicles and identified γ2 clathrin-coated vesicles in mice. Ubiquitous σ1A and tissue-specific σ1B adaptins bind γ2 and γ1. σ1B knockout in mice does not effect γ1/σ1A AP-1 levels, but γ2/σ1A AP-1 levels are increased in brain and adipocytes. Also γ2 is essential in development. In zebrafish AP-1/γ2 and AP-1/γ1 fulfill different, essential functions in brain and the vascular system.
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia Medical School, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zizioli
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Goettingen, Georg-August-University Göttingen, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Geumann
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Goettingen, Georg-August-University Göttingen, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Kratzke
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Goettingen, Georg-August-University Göttingen, Germany.
authors.forename: Ratnakar
authors.initials: R
authors.lastname: Mishra
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia Medical School, Italy.
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Borsani
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia Medical School, Italy; ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Finazzi
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Goettingen, Georg-August-University Göttingen, Germany.
authors.forename: Ermes
authors.initials: E
authors.lastname: Candiello
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Goettingen, Georg-August-University Göttingen, Germany. Electronic address: pschu@gwdg.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Schu
mesh_terms: D033982:Adaptor Protein Complex gamma Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034002:Adaptor Protein Complex sigma Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000254:growth & development / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002460:Cell Line; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D021381:Protein Transport / Q000235:genetics; D015398:Signal Transduction; D022161:Transport Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D015027:Zebrafish; D021601:trans-Golgi Network / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D033982:Adaptor Protein Complex gamma Subunits; D034002:Adaptor Protein Complex sigma Subunits; D002966:Clathrin; D020033:Protein Isoforms
keywords: AP-1; Clathrin; Vesicular transport; γ1; γ2