Reactome | SAMD8 transfers phosphatidyl from PE onto C16DH CER

SAMD8 transfers phosphatidyl from PE onto C16DH CER

Stable Identifier

R-HSA-8959462

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, endoplasmic reticulum lumen

ReviewStatus

5/5

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SAMD8 transfers phosphatidyl from PE onto C16DH CER

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Sphingolipids such as sphingomyelin (SM) are essential components of cellular membranes and dynamic regulators of many cellular processes in most organisms. Ceramides constitute the backbone of all sphingolipids and are synthesized on the cytosolic surface of the endoplasmic reticulum (ER) and then transported to the Golgi for conversion to SM. The ER-membrane resident protein sphingomyelin synthase-related protein 1 (SAMD8) catalyzes the synthesis of the SM analog ceramide phosphoethanolamine (CPE) in the ER lumen. SAMD8 only produces trace amounts of CPE, but blocking its catalytic activity causes a substantial rise in ER ceramide levels and a structural collapse of the early secretory pathway. SAMD8 is, therefore, a key regulator of ceramide homeostasis, functioning as a sensor rather than a converter of ceramides in the ER (Vacaru et al., 2009). SAMD8 self-associates into ER-resident trimers and hexamers (Cabukusta et al., 2017). The biological role of the produced CPE in humans needs to be better defined. However, it is the main sphingolipid in arthropods and some protozoa and bacteria (see review by Panewska et al., 2019).

Literature References

PubMed ID	Title	Journal	Year
28120887	ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain Cabukusta, B, Kol, M, Kneller, L, Hilderink, A, Bickert, A, Mina, JG, Korneev, S, Holthuis, JC	Sci Rep	2017
19506037	Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER Vacaru, AM, Tafesse, FG, Ternes, P, Kondylis, V, Hermansson, M, Brouwers, JF, Somerharju, P, Rabouille, C, Holthuis, JC	J. Cell Biol.	2009
31067435	Ceramide phosphoethanolamine, an enigmatic cellular membrane sphingolipid Panevska, A, Skočaj, M, Križaj, I, Maček, P, Sepčić, K	Biochim Biophys Acta Biomembr	2019