Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis

Saito, Atsushi; Hino, Shinjiro; Murakami, Tomohiko; Kanemoto, Soshi; Kondo, Shinichi; Saitoh, Masahiro; Nishimura, Riko; Yoneda, Toshiyuki; Furuichi, Tatsuya; Ikegawa, Shiro; Ikawa, Masahito; Okabe, Masaru; Imaizumi, Kazunori

doi:10.1038/ncb1962

Cited by 189 publications

(297 citation statements)

References 26 publications

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“…Involving differentiation, chondrocytes secrete cartilage ECM proteins at about 4 day after the culture. Corresponding with the secretion, ER stress markers, Bip, Pdi, Grp94, and Edem are slightly upregulated at days 4 and 7 in the micromass culture, indicating that mild ER stress is induced in chondrocytes during their normal differentiation (20). Induction of Bbf2h7 mRNA and RIP of BBF2H7 just begin at this stage in differentiation of the chondrocytes.…”

Section: Chondrocyte Differentiation and Er Stressmentioning

confidence: 89%

“…Interestingly, each of them commonly contains the consensus sequence for cleavage by site-1 protease (S1P) and site-2 protease (S2P) in its lumenal segment, indicating that they are processed at transmembrane regions by regulated intramembrane proteolysis (RIP) (18). OASIS family proteins reveal unique cell or tissue-specific expression patterns, that is, OASIS, BBF2H7, CREBH, and AIbZIP are preferentially expressed in osteoblasts and astrocytes (11,19), chondrocytes (20), liver cells (21), and prostate and testis (22), respectively.…”

Section: Transmembrane Bzip Transcription Factors Activated By Regulamentioning

confidence: 99%

“…Where it differs from OASIS is in its expression patterns. On examining the tissue localization of BBF2H7, it is most strongly expressed is in the proliferating zone of the cartilage in developing long bones (20). Bbf2h7 is also expressed in the lungs, spleen, gonad and nervous system (12) although not expressed at all in osseous tissues (20).…”

Section: Er Stress Transducer Bbf2h7 and Chondrogenesis Bbf2h7 2/2 MImentioning

confidence: 99%

“…Bbf2h7 2/2 mice reveal severe chondrodysplasia and die by suffocation shortly after birth because of an immature chest cavity (20). In Bbf2h7 -/-cartilage, the typical columnar structure is lack in the proliferating zone and the size of the hypertrophic zone is decreased involving a significant reduction of extracellular matrix (ECM) proteins.…”

Section: Er Stress Transducer Bbf2h7 and Chondrogenesis Bbf2h7 2/2 MImentioning

confidence: 99%

“…A micromass culture that is prepared from the limbs of E11.5 mice is well used for the analysis on mechanisms of chondrocyte differentiation (20,34). With this culture system, mesenchymal cells gradually differentiate into mature chondrocytes with the expression of mature chondrocyte markers, Collagen type 2 (Col2), Comp, Aggrican, Ihh, and Pthr1.…”

Section: Chondrocyte Differentiation and Er Stressmentioning

confidence: 99%

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Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors

et al. 2011

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SummaryThe endoplasmic reticulum (ER) plays role in the maintenance of numerous aspects of cellular and organismal homeostasis by folding, modifying, and exporting nascent secretory and transmembrane proteins. Failure of the ER's adaptive capacity results in accumulation of unfolded or malfolded proteins in the ER lumen (ER stress). To avoid cellular damage, mammalian cells activate the specific signals from the ER to the cytosol or nucleus to enhance the capacity for protein folding, attenuate the synthesis of proteins, and degrade unfolded proteins. These signaling pathways are collectively known as the unfolded protein response (UPR). The canonical branches of the UPR are mediated by three ER membrane-bound proteins, PERK, IRE1, and ATF6. These ER stress transducers basically play important roles in cell survival after ER stress. Recently, novel types of ER stress transducers, OASIS family members that share a region of high sequence similarity with ATF6 have been identified. They have a transmembrane domain, which allows them to associate with the ER, and possess a transcription-activation domain and a bZIP domain. OASIS family proteins include OASIS, BBF2H7, CREBH, AIbZIP, and Luman. Despite the structural similarities among OASIS family proteins and ATF6, differences in activating stimuli, tissue distribution, and response element binding indicate specialized functions of each member on regulating the UPR in the specific organs and tissues. Here, we summarize our current understanding of biochemical characteristics and in vivo functions of OASIS family proteins, particularly focusing on OASIS and BBF2H7. A growing body of new works suggests that the UPR branches regulated by OASIS family members play essential roles in cell differentiation and maturation or maintenance of basal cellular homeostasis in mammals.

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Section: Chondrocyte Differentiation and Er Stressmentioning

confidence: 89%

Section: Transmembrane Bzip Transcription Factors Activated By Regulamentioning

confidence: 99%

Section: Er Stress Transducer Bbf2h7 and Chondrogenesis Bbf2h7 2/2 MImentioning

confidence: 99%

Section: Er Stress Transducer Bbf2h7 and Chondrogenesis Bbf2h7 2/2 MImentioning

confidence: 99%

Section: Chondrocyte Differentiation and Er Stressmentioning

confidence: 99%

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Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors

et al. 2011

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Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in MBTPS1

Carvalho

Speck‐Martins

Brum

et al. 2020

American J of Med Genetics Pt A

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Variants in MBTPS1 (membrane-bound transcription factor peptidase, site 1) encoding the protein convertase site-1 protease (S1P) were recently reported in a single individual with skeletal dysplasia and elevated plasma lysosomal enzymes. Here, we report the second individual with this newly described autosomal recessive spondyloepiphyseal dysplasia (OMIM #618392), presenting severe growth retardation, cataract and dysmorphic features, mainly retromicrognathia. Epilepsy and craniosynostosis were novel findings in our proband. She was found to be homozygous for a novel nonsense variant p.Trp983Ter in MBTPS1. In addition, she had normal levels of lysosomal enzyme activity in leukocytes but elevated levels in plasma. Our description confirms the existence of this new skeletal dysplasia and expands the phenotype and genotype of the disease.

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Genetic Disorders of the Extracellular Matrix

Lamandé

Bateman

2019

The Anatomical Record

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Mutations in the genes for extracellular matrix (ECM) components cause a wide range of genetic connective tissues disorders throughout the body. The elucidation of mutations and their correlation with pathology has been instrumental in understanding the roles of many ECM components. The pathological consequences of ECM protein mutations depend on its tissue distribution, tissue function, and on the nature of the mutation. The prevalent paradigm for the molecular pathology has been that there are two global mechanisms. First, mutations that reduce the production of ECM proteins impair matrix integrity largely due to quantitative ECM defects. Second, mutations altering protein structure may reduce protein secretion but also introduce dominant negative effects in ECM formation, structure and/or stability. Recent studies show that endoplasmic reticulum (ER) stress, caused by mutant misfolded ECM proteins, makes a significant contribution to the pathophysiology. This suggests that targeting ER-stress may offer a new therapeutic strategy in a range of ECM disorders caused by protein misfolding mutations. Anat Rec,

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Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis

Cited by 189 publications

References 26 publications

Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors

Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors

Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in MBTPS1

Genetic Disorders of the Extracellular Matrix

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