Van Galen et al. reveal that the lipid sphingomyelin (SM) organizes proteins into functional domains at the trans-Golgi network.

Along with cholesterol, SM forms rigid, liquid-ordered domains within cell membranes, but whether these domains control cellular functions by clustering specific transmembrane proteins together is unclear. Van Galen et al. perturbed SM homeostasis by treating cells with a short-chain ceramide, d-cer-C6, that is converted by enzymes at the trans-Golgi network and plasma membrane into a short-chain SM incapable of forming liquid-ordered domains.

d-cer-C6 treatment quickly disrupted the organization of Golgi membranes. Golgi proteins such as sialyltransferase and TGN46 segregated away from each other instead of colocalizing at the trans-Golgi network. This physical separation prevented sialyltransferase from glycosylating TGN46, demonstrating that SM-based membrane domains organize the components of simple biochemical reactions. SM may also promote more complex processes, such as vesicle biogenesis, by clustering multiple proteins into the same domain.

d-cer-C6 disrupted Golgi form as well as function, causing the normally flat cisternae to curl up into concentric rings. Rigid, SM-rich membrane domains may therefore concentrate Golgi-resident enzymes in the flattened center of Golgi cisternae. Substrate proteins, in contrast, would only transiently associate with these domains as they move through the Golgi on their journey along the secretory pathway. Senior author Vivek Malhotra now wants to investigate how the transmembrane regions of Golgi enzymes and their substrates determine their affinities for SM-rich membrane domains.

van Galen
, et al
J. Cell Biol
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Author notes

Text by Ben Short