FAM20A binds to and regulates FAM20C localization.
Mutations in the Family with sequence similarity (FAM) 20 gene family are associated with mineralized tissue phenotypes in humans. Among these genes, FAM20A mutations are associated with Amelogenesis Imperfecta (AI) with gingival hyperplasia and nephrocalcinosis, while FAM20C mutations cause Raine syndrome, exhibiting bone and craniofacial/dental abnormalities. Although it has been demonstrated that Raine syndrome associated-FAM20C mutants prevented FAM20C kinase activity and secretion, overexpression of the catalytically inactive D478A FAM20C mutant was detected in both cell extracts and the media. This suggests that FAM20C secretion doesn't require its kinase activity, and that another molecule(s) may control the secretion. In this study, we found that extracellular FAM20C localization was increased when wild-type (WT), but not AI-forms of FAM20A was co-transfected. On the other hand, extracellular FAM20C was absent in the conditioned media of mouse embryonic fibroblasts (MEFs) derived from Fam20a knock-out (KO) mouse, while it was detected in the media from WT MEFs. We also showed that cells with the conditioned media of Fam20a WT MEFs mineralized, but those with the conditioned media of KO MEFs failed to mineralize in vitro. Our data thus demonstrate that FAM20A controls FAM20C localization that may assist in the extracellular function of FAM20C in mineralized tissues.
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, United States of America.
Yoshio
Y
Ohyama
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, United States of America.
Ju-Hsien
JH
Lin
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, United States of America.|Research Unit of Mineralized Tissue, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Nattanan
N
Govitvattana
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, United States of America.
I-Ping
IP
Lin
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, United States of America.
Sundharamani
S
Venkitapathi
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, United States of America.
Ahmed
A
Alamoudi
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, United States of America.
Dina
D
Husein
Division of Microbiology, Kobe University Graduate School of Medicine, Kobe, Japan.
Chunying
C
An
Division of Microbiology, Kobe University Graduate School of Medicine, Kobe, Japan.
Hak
H
Hotta
Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Masaru
M
Kaku
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, United States of America.
Yoshiyuki
Y
Mochida