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

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Item Type:	Article
Title:	The progressive ankyloses protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface
Creators Name:	Seifert, W., Posor, Y., Schu, P., Stenbeck, G., Mundlos, S., Klaassen, S., Nürnberg, P., Haucke, V., Kornak, U. and Kühnisch, J.
Abstract:	Dominant or recessive mutations in the progressive ankylosis gene ANKH have been linked with familial chondrocalcinosis (CCAL2), craniometaphyseal dysplasia (CMD), and mental retardation, deafness, 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.
Keywords:	Cell Membrane, Clathrin, Clathrin-Coated Vesicles, Endocytosis, Fibroblasts, HeLa Cells, Phosphate Transport Proteins, Transferrin, trans-Golgi Network
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	25
Number:	17
Page Range:	3836-3848
Date:	1 September 2016
Additional Information:	Copyright © The Authors 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
Official Publication:	https://doi.org/10.1093/hmg/ddw230
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