Loss of Fam20c causes defects in the acinar and duct structure of salivary glands in mice

Abstract

Family with sequence similarity 20-member C (FAM20C), a recently characterized Golgi kinase, performs numerous biological functions by phosphorylating more than 100 secreted proteins. However, the role of FAM20C in the salivary glands remains undefined. The present study demonstrated that FAM20C is mainly located in the cytoplasm of duct epithelial cells in the salivary glands. Fam20c f/f ; Mmtv-Cre mice were created in which Fam20c was inactivated in the salivary gland cells and observed that the number of ducts and the ductal cross-sectional area increased significantly, while the number of acinar cells was reduced. The granular convoluted tubules (GCTs) exhibited an accumulation of aberrant secretory granules, along with a reduced expression and altered distribution patterns of β nerve growth factor, α-amylase and bone morphogenetic protein (BMP) 4. This abnormality suggested that the GCT cells were immature and exhibited defects in developmental and secretory functions. In accordance with the morphological alterations and the reduced number of acinar cells, FAM20C deficiency in the salivary glands significantly decreased the salivary flow rate. The Na + , Cl − and K + concentrations in the saliva were all significantly increased due to dysfunction of the ducts. Furthermore, Fam20c deficiency significantly increased BMP2 and BMP7 expression, decreased BMP4 expression, and attenuated the canonical and noncanonical BMP signaling pathways in the salivary glands. Collectively, the results of the present study demonstrate that FAM20C is a key regulator of acinar and duct structure and duct maturation and provide a novel avenue for investigating novel therapeutic targets for oral diseases including xerostomia.

Prognostic and immunological role of Fam20C in pan-cancer

“…Fam20C is identified as Golgi casein kinase, which is expressed in a variety of tissues, including mineralized and non-mineralized tissues and body fluids [ 15 , 16 , 49 ]. Protein within Ser-X-Glu/pSer motif is phosphorylated by Fam20C in some 75% of human plasma and cerebrospinal fluid phosphoproteins.…”

Bulk RNA-seq and scRNA-seq analysis reveal an activation of immune response and compromise of secretory function in major salivary glands of obese mice

“…S5 B). Annotation of these 17 clusters with feature genes [1] , [7] , [8] , [9] , [10] , [32] , [33] , [34] , [35] , [36] , [37] (Supplementary Table S12 and S13 ) identified serous (cluster 4), seromucous (cluster 6) and mucous (cluster 11) three types of acinar cells, and striated (cluster 1), intercalated (cluster 7), excretory (cluster 8) and GCT (cluster 9) four types of ductal cells ( Fig. 7 A, Supplementary Fig.…”

FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes

“…Functionally, it causes duct dysfunctions manifested by a reduced salivary flow rate and elevation of the Na + , Cl − and K + concentrations. In addition, it affects the expression of BMP2 and BMP7 proteins (BMP signaling pathways) [ 134 ]. These results link FAM20C to other biological roles, as well as a possible role in salivary glands in RS.…”