Disruption of distal appendage protein CEP164 causes skeletal malformation in mice.

Autor: Yamaguchi H; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Kitami M; Center for Advanced Oral Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Li M; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Kinesiology, Rice University Wiess School of Natural Science, Houston, TX, USA., Swaminathan S; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA., Darabi R; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA; Institute of Muscle Biology and Cachexia, University of Houston, Houston, TX, USA., Takemaru KI; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA., Komatsu Y; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Graduate Program in Genetics and Epigenetics, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA. Electronic address: Yoshihiro.Komatsu@uth.tmc.edu.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 31; Vol. 741, pp. 151063. Date of Electronic Publication: 2024 Nov 26.
DOI: 10.1016/j.bbrc.2024.151063
Abstrakt: The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis. However, the role of the ciliary proteins responsible for initiating cilium assembly in skeletal development remains unknown. Here, we investigate the function of centrosomal protein of 164 kDa (CEP164), a key ciliogenesis regulator that localizes at the distal appendages of the mother centriole, during skeletal development in mice. Interestingly, the mesodermal cell-specific Cep164 deletion resulted in severe bone defects and osteoblast-specific deletion of Cep164 affected bone development. In contrast, chondrocyte-specific Cep164 deletion did not cause overt skeletal abnormalities, indicating that CEP164 functions in a cell type-specific manner within skeletal tissues. Importantly, Cep164-mutant osteoblasts not only displayed a lack of cilia but also showed an increased number of γH2AX-positive cells, indicating the involvement of defective DNA damage response in the etiology of skeletal lesions of Cep164-mutant mice. These results demonstrate that CEP164 has both ciliary and non-ciliary functions to control osteoblast growth and survival. Our study therefore reveals a novel understanding of the pathogenesis of skeletal ciliopathies associated with CEP164 dysfunction.
Competing Interests: Declaration of competing interest All authors state that they have no conflicts of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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