Seifert, W;
Posor, Y;
Schu, P;
Stenbeck, G;
Mundlos, S;
Klaassen, S;
Nuernberg, P;
... Kuehnisch, J; + view all
(2016)
The progressive ankylosis protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface.
Human Molecular Genetics
, 25
(17)
pp. 3836-3848.
10.1093/hmg/ddw230.
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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.
| Type: | Article |
|---|---|
| Title: | The progressive ankylosis protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/hmg/ddw230 |
| Publisher version: | https://doi.org/10.1093/hmg/ddw230 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Genetics & Heredity, Inorganic Pyrophosphate, Craniometaphyseal Dysplasia, Recycling Endosomes, Plasma-Membrane, Cell-Surface, Brefeldin-A, Mutations, Transferrin, Disease, Binding |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10051559 |
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