title: AP1S1 defect causing MEDNIK syndrome: a new adaptinopathy associated with defective copper metabolism.
abstract: MEDNIK (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratodermia) syndrome has been recently described as a new disorder of copper metabolism. This multisystem disease combines clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver copper overload is treatable using zinc acetate therapy. MEDNIK syndrome is caused by mutation of the AP1S1 gene, which codes for the σ1A subunit of adaptor protein complex 1, and directs intracellular trafficking of copper pumps ATP7A and ATP7B. Adaptor protein complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. A growing number of diseases have been associated with mutations in genes coding for adaptor protein complexes subunits and we propose for them the term adaptinopathies, as a new organic category of disorders of intracellular trafficking, which offers the opportunity to dissect the mechanisms involved in the crosstalk between the Golgi apparatus and the other organelles.
authors.affiliation: Unit of Metabolism, Department of Pediatrics, Bambino Gesu Children's Hospital, Rome, Italy; Section on Translational Neuroscience, Molecular Medicine Program, NICHD/NIH, Bethesda, Maryland.
authors.forename: Diego
authors.initials: D
authors.lastname: Martinelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
mesh_terms: D000220:Adaptation, Biological; D033961:Adaptor Protein Complex 1 / Q000235:genetics*; D034002:Adaptor Protein Complex sigma Subunits / Q000235:genetics*; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics*; D021381:Protein Transport / Q000235:genetics; D013577:Syndrome; D019345:Zinc Acetate / Q000627:therapeutic use
chemical_list: C438983:AP1S1 protein, human; D033961:Adaptor Protein Complex 1; D034002:Adaptor Protein Complex sigma Subunits; D033942:Adaptor Proteins, Vesicular Transport; D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D019345:Zinc Acetate
keywords: AP1S1; MEDNIK syndrome; adaptinopathies; adaptor protein complexes