This gene encodes a member of the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. This group of proteins is characterized by a polybasic proteolytic processing site that is cleaved to produce a mature protein containing seven conserved cysteine residues. Members of this family are regulators of cell growth and differentiation in both embryonic and adult tissues. Studies in yeast suggest that the encoded protein is involved in aging. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1.[3]
CerS1/GDF1 mRNA is strongly expressed in muscle and brain, and was also found in heart and lung.[7] Within the brain, CerS1 is the primary CerS expressed in most neurons. In white matter, it can only be found in low levels.[5][8]
In a recent experiment performed in mice in 2012, ablation of neuronal CerS1 decreased levels of sphingolipids, hexosylceramides, and sphingomyelin. Although the brains in these mice appeared to develop normally, researchers observed atrophy of the cerebellum, and Purkinje neurons appeared to degenerate. Granule cells also showed a 6 times increased rate of apoptosis. Behaviorally, the mice expressed motor and neurophysiological impairment.[4]
Structure
Unlike other mammalian ceramides, CerS1 does not appear to have a Hox-like domain. It is functionally and structurally distinct from other CerS and is found in an entirely different branch of the phylogenetic tree.[5]
Clinical significance
On application of various stresses, CerS1 turns over rapidly by ubiquitination and proteasomal degradation, suggesting that it has a short half life.[5]
↑Riebeling C, Allegood JC, Wang E, Merrill AH Jr, Futerman AH (Oct 2003). "Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors". J Biol Chem. 278 (44): 43452–9. doi:10.1074/jbc.M307104200. PMID12912983.
↑Becker I, Wang-Eckhardt L, Yaghootfam A, Gieselmann V, Eckhardt M (February 2008). "Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2". Histochemistry and Cell Biology. 129 (2): 233–41. doi:10.1007/s00418-007-0344-0. PMID17901973.
Koybasi S, Senkal CE, Sundararaj K, et al. (2004). "Defects in cell growth regulation by C18:0-ceramide and longevity assurance gene 1 in human head and neck squamous cell carcinomas". J. Biol. Chem. 279 (43): 44311–9. doi:10.1074/jbc.M406920200. PMID15317812.
Grimwood J, Gordon LA, Olsen A, et al. (2004). "The DNA sequence and biology of human chromosome 19". Nature. 428 (6982): 529–35. doi:10.1038/nature02399. PMID15057824.
Venkataraman K, Riebeling C, Bodennec J, et al. (2002). "Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro)ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells". J. Biol. Chem. 277 (38): 35642–9. doi:10.1074/jbc.M205211200. PMID12105227.