CMP-Sialic Acid Transporter

Abstract

The compartmentalization of cytidine 5′-monophosphate (CMP)-sialic acid synthesis in the cell nucleus (for review Kean 1991; Munster et al. 1998) and its metabolism in the lumen of the Golgi apparatus demonstrates that a system that transports the nucleotide sugar across the Golgi membrane is required. This function is accomplished by the CMP-sialic acid transporter (CST), a highly hydrophobic type III membrane protein (Hirschberg and Snider 1987; Hirschberg et al. 1998). The membrane topology has been identified for murine CST (Eckhardt et al. 1999), but so far no information is available on the tertiary and potential quaternary structure of the protein. The CST provides a key element in the cellular sialylation pathway, and defects in the CST gene lead to drastically reduced levels (Stanley and Siminovitch 1976; Briles et al. 1977) or complete loss (Eckhardt et al. 1996) of sialylated glycoconjugates. The lack of clinical manifestations caused by defects in the CST gene suggests that mutations in this important structure are lethal.