Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The PDZ-domain-containing sorting nexin 27 (SNX27) promotes recycling of internalized transmembrane proteins from endosomes to the plasma membrane by linking PDZ-dependent cargo recognition to retromer-mediated transport. Here, we employed quantitative proteomics of the SNX27 interactome and quantification of the surface proteome of SNX27- and retromer-suppressed cells to dissect the assembly of the SNX27 complex and provide an unbiased global view of SNX27-mediated sorting. Over 100 cell surface proteins, many of which interact with SNX27, including the glucose transporter GLUT1, the Menkes disease copper transporter ATP7A, various zinc and amino acid transporters, and numerous signalling receptors, require SNX27-retromer to prevent lysosomal degradation and maintain surface levels. Furthermore, we establish that direct interaction of the SNX27 PDZ domain with the retromer subunit VPS26 is necessary and sufficient to prevent lysosomal entry of SNX27 cargo. Our data identify the SNX27-retromer as a major endosomal recycling hub required to maintain cellular nutrient homeostasis.
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PMID:A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport. 2363 23

Epilepsies associated with inborn errors of metabolism (IEM) represent a major challenge. Seizures rarely dominate the clinical presentation, which is more frequently associated with other neurological symptoms, such as hypotonia and/or cognitive disturbances. Although epilepsy in IEM can be classified in various ways according to pathogenesis, age of onset, or electroclinical presentation, the most pragmatic approach is determined by whether they are accessible to specific treatment or not. The main potentially treatable causes comprise vitamin B6 (pyridoxine deficiency), biotine, and GLUT1 deficiency (GLUT1DS) syndromes. Folinic acid-dependent seizures are allelic with pyridoxine dependency. Incompletely treatable IEMs include pyridoxal phosphate, serine, and creatine deficiencies. The main IEMs that present with epilepsy but offer no specific treatment are nonketotic hyperglycinemia, mitochondrial disorders, sulfite oxidase deficiency, ceroid-lipofuscinosis, Menkes disease, and peroxisomal disorders.
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PMID:Epilepsy in inborn errors of metabolism. 2362 1