Cohen syndrome-associated protein, COH1, is a novel, giant Golgi matrix protein required for Golgi integrity.

[cohen syndrome]

Loss -of-function mutations in the gene COH 1 , also known as VPS 13 B , lead to autosomal recessive Cohen syndrome . However , the cellular distribution and function of the encoded protein COH 1 (3997 amino acids ), which lacks functional homologies to other mammalian proteins , have remained enigmatic . We show here that COH 1 is a peripheral Golgi membrane protein that strongly co -localizes with the cis-Golgi matrix protein GM 130 . Consistent with its subcellular localization , COH 1 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 COH 1 as a Golgi-associated matrix protein required for Golgi integrity .