The progressive ankylosis protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface.

Content Provider	Semantic Scholar
Author	Seifert, Wenke Schu, Peter Stenbeck, Gudrun Mundlos, Stefan Klaassen, Sabine Nürnberg, Peter Haucke, Volker Kornak, Uwe Kühnisch, Jirko
Copyright Year	2016
Abstract	Dominant or recessive mutations in the progressive ankylosis gene ANKH have been linked to familial chondrocalcinosis (CCAL2), craniometaphyseal dysplasia (CMD), mental retardation, deafness and ankylosis syndrome (MRDA). The function of the encoded membrane protein ANK in cellular compartments other than the plasma membrane is unknown. Here, we show that ANK localizes to the trans-Golgi network (TGN), clathrin-coated vesicles and the plasma membrane. ANK functionally interacts with clathrin and clathrin associated adaptor protein (AP) complexes as loss of either protein causes ANK dispersion from the TGN to cytoplasmic endosome-like puncta. Consistent with its subcellular localization, loss of ANK results in reduced formation of tubular membrane carriers from the TGN, perinuclear accumulation of early endosomes and impaired transferrin endocytosis. Our data indicate that clathrin/AP-mediated cycling of ANK between the TGN, endosomes, and the cell surface regulates membrane traffic at the TGN/endosomal interface. These findings suggest that dysfunction of Golgi-endosomal membrane traffic may contribute to ANKH-associated pathologies.
Starting Page	3836
Ending Page	3848
Page Count	13
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://discovery.ucl.ac.uk/10051559/1/160727_Hum.%20Mol.%20Genet.-2016-Seifert-hmg_ddw230.pdf
Alternate Webpage(s)	https://pure.mpg.de/rest/items/item_2463513_2/component/file_2477016/content?download=true
PubMed reference number	27466194v1
Alternate Webpage(s)	https://doi.org/10.1093/hmg/ddw230
DOI	10.1093/hmg/ddw230
Journal	Human molecular genetics
Volume Number	25
Issue Number	17
Language	English
Access Restriction	Open
Subject Keyword	ANK1 gene ANKH gene Adaptor Proteins, Signal Transducing Adenomatous Polyposis Coli Anatomical compartments Calcium pyrophosphate arthropathy Calcium pyrophosphate deposition disease Cell surface Christ-Siemens-Touraine syndrome Clathrin Clathrin-Coated Vesicles Coated vesicle Endosomes Golgi Apparatus Membrane Protein Traffic Membrane Proteins Mental Retardation Mutation Plasma membrane Schwartz-Lelek syndrome Tissue membrane Vesicle (morphologic abnormality) positive regulation of ER to Golgi vesicle-mediated transport trans-Golgi Network
Content Type	Text
Resource Type	Article