Molecular Cloning of Mouse Homologue of Enamel Protein C4orf26 and Its Phosphorylation by FAM20C

Govitvattana, Nattanan; Kaku, Masaru; Ohyama, Yoshio; Jaha, Haytham; Lin, I-Ping; Mochida, Hanna; Pavasant, Prasit; Mochida, Yoshiyuki

doi:10.1007/s00223-021-00847-y

Cited by 1 publication

(2 citation statements)

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“…Secretory ameloblasts transition into maturation ameloblasts to perform stage-specific functions with stage-specific gene expressions 29 . The known maturation stage markers of ameloblasts include Odam 19 , 30 , Odaph 9 , 10 and Klk4 31 , while secretory stage markers are Mmp20 32 , Amelogenin 33 and Enamelin 34 . There are two major ameloblast-like cell lines frequently used and characterized by the enamel research community.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in several proteinases including MMP20 and KLK4 lead to the improper enamel matrix protein processing and degradation and poor enamel mineralization seen in enamel hypomaturation phenotypes 4 . To date, hypomaturation AI have been associated with mutations in at least four genes that do not encode enamel proteinases, such as pH-sensing G-protein-coupled receptor (GPR68) 5 , 6 , potassium-dependent sodium/calcium exchanger (SLC24A4) 7 , 8 , enamel matrix protein phosphorylated by FAM20C (ODAPH) 9 , 10 and WDR72 11 .…”

Section: Introductionmentioning

confidence: 99%

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Identification of the C-terminal region in Amelogenesis Imperfecta causative protein WDR72 required for Golgi localization

Husein

Alamoudi

Ohyama

et al. 2022

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Amelogenesis Imperfecta (AI) represents a group of hereditary conditions that manifest tooth enamel defects. Several causative mutations in the WDR72 gene have been identified and patients with WDR72 mutations have brown (or orange-brown) discolored enamel, rough enamel surface, early loss of enamel after tooth eruption, and severe attrition. Although the molecular function of WDR72 is not yet fully understood, a recent study suggested that WDR72 could be a facilitator of endocytic vesicle trafficking, which appears inconsistent with the previously reported cytoplasmic localization of WDR72. Therefore, the aims of our study were to investigate the tissues and cell lines in which WDR72 was expressed and to further determine the sub-cellular localization of WDR72. The expression of Wdr72 gene was investigated in mouse tissues and cell lines. Endogenous WDR72 protein was detected in the membranous fraction of ameloblast cell lines in addition to the cytosolic fraction. Sub-cellular localization studies supported our fractionation data, showing WDR72 at the Golgi apparatus, and to a lesser extent, in the cytoplasmic area. In contrast, a WDR72 AI mutant form that lacks its C-terminal region was exclusively detected in the cytoplasm. In addition, our studies identified a putative prenylation/CAAX motif within the last four amino acids of human WDR72 and generated a WDR72 variant, called CS mutant, in which the putative motif was ablated by a point mutation. Interestingly, mutation of the putative CAAX motif impaired WDR72 recruitment to the Golgi. Cell fractionation assays confirmed subcellular distribution of wild-type WDR72 in both cytosolic and membranous fractions, while the WDR72 AI mutant and CS mutant forms were predominantly detected in the cytosolic fraction. Our studies provide new insights into the subcellular localization of WDR72 and demonstrate a critical role for the C-terminal CAAX motif in regulating WDR72 recruitment to the Golgi. In accordance with structural modelling studies that classified WDR72 as a potential vesicle transport protein, our findings suggest a role for WDR72 in vesicular Golgi transport that may be key to understanding the underlying cause of AI.

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