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Although the first phosphorylated protein casein (casein) was reported in 1883, it was not until 2012 that the first secretory pathway protein kinase Fam20C was identified, which catalyzes the phosphorylation of most secreted proteins including casein
.
Recent studies have shown that Fam20C is involved in the regulation of biomineralization, cell adhesion and migration, prohormone processing, lipid homeostasis, protein transport, and endoplasmic reticulum homeostasis, and many other life processes
On August 5, 2021, "Proceedings of the National Academy of Sciences" (PNAS) published online a research paper "Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization" by Wang Zhizhen's research group at the Institute of Biophysics, Chinese Academy of Sciences
.
The study identified the membrane protein properties of the secretory pathway kinase Fam20C, and found that the Golgi protease site-1 protease (S1P) is responsible for cutting and processing Fam20C and promoting its activation and secretion, revealing the role of this regulatory mechanism in the process of osteoblast differentiation.
Based on the previous findings that Fam20C regulates endoplasmic reticulum redox homeostasis (EMBO J, 2018) and protein homeostasis (EMBO J, 2020), researchers found that Fam20C is not a soluble protein in the lumen of the secretory pathway as previously thought , But a type II membrane protein
.
After synthesis of the endoplasmic reticulum, Fam20C is transported to the Golgi apparatus by COP II vesicles, and is anchored on the Golgi apparatus by its N-terminal transmembrane helix
The functional defect of Fam20C is closely related to the bone dysplasia disease Lane syndrome.
S1P has also been reported to be involved in the process of bone development, but its molecular mechanism has been unclear
.
The researchers used the osteoblast differentiation model to clarify that S1P-mediated Fam20C processing and maturation is very important for the phosphorylation of secreted calcium binding proteins such as osteopontin, and this event is indispensable for the process of biomineralization
Picture: Protease S1P cleavage processing secretory pathway kinase Fam20C promotes biomineralization
Article link: https:// align="justify" >
(Contribution: Wang Zhizhen Research Group)