title: Cohen syndrome-associated protein, COH1, is a novel, giant Golgi matrix protein required for Golgi integrity.
abstract: Loss-of-function mutations in the gene COH1, also known as VPS13B, lead to autosomal recessive Cohen syndrome. However, the cellular distribution and function of the encoded protein COH1 (3997 amino acids), which lacks functional homologies to other mammalian proteins, have remained enigmatic. We show here that COH1 is a peripheral Golgi membrane protein that strongly co-localizes with the cis-Golgi matrix protein GM130. Consistent with its subcellular localization, COH1 depletion using RNAi causes fragmentation of the Golgi ribbon into ministacks. Disruption of Golgi organization observed in fibroblasts from Cohen syndrome patients suggests that Golgi dysfunction contributes to Cohen syndrome pathology. In conclusion, our findings establish COH1 as a Golgi-associated matrix protein required for Golgi integrity.
authors.affiliation: Cologne Center for Genomics, Universität zu Köln, 50931 Köln, Germany. wenke.seifert@charite.de
authors.forename: Wenke
authors.initials: W
authors.lastname: Seifert
authors.forename: Jirko
authors.initials: J
authors.lastname: Kühnisch
authors.forename: Tanja
authors.initials: T
authors.lastname: Maritzen
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
authors.forename: Volker
authors.initials: V
authors.lastname: Haucke
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
mesh_terms: D002658:Developmental Disabilities / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005385:Fingers / Q000002:abnormalities / Q000473:pathology; D017353:Gene Deletion; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007425:Intracellular Membranes / Q000378:metabolism* / Q000473:pathology; D008831:Microcephaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009123:Muscle Hypotonia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009216:Myopia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins