Back to Search
Start Over
The progressive ankylosis protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface
- Source :
- Human Molecular Genetics
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
Cytoplasm
Tissue Membrane
Endosome
Ankylosis
Golgi Apparatus
Adaptor Signalling Protein
Endosomes
Trans-Golgi Network
Biology
Endocytosis
Clathrin
Cell membrane
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Complex
Genetics
medicine
Humans
Phosphate Transport Proteins
Molecular Biology
Genetics (clinical)
Vesicle
Cell Membrane
Transferrin
Signal transducing adaptor protein
Clathrin-Coated Vesicles
General Medicine
Fibroblasts
Golgi apparatus
Cell biology
Transferrin Receptors
030104 developmental biology
medicine.anatomical_structure
Biochemistry
Membrane protein
Genes
Mutation
biology.protein
symbols
Calcium Pyrophosphate Deposition Disease
030217 neurology & neurosurgery
HeLa Cells
trans-Golgi Network
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....8e74cb316d274fded3e6bd592df0d794