The <i>Caenorhabditis elegans</i> SMOC-1 Protein Acts Cell Nonautonomously To Promote Bone Morphogenetic Protein Signaling

DeGroot, Melisa S; Shi, Herong; Eastman, Alice; McKillop, Alexandra N; Liu, Jun

doi:10.1534/genetics.118.301805

Cited by 11 publications

(31 citation statements)

References 71 publications

(85 reference statements)

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“…[18] Indeed, the C. elegans SMOC1 homolog acted as a positive modulator of the BMP signaling during development of C. elegans , and human SMOC1 and SMOC2 transgenes could each partially rescue phenotypes of SMOC1 mutants in worms, suggesting that SMOC1 modulation of BMP signaling was evolutionarily conserved. [24] The most recent findings of the function and molecular mechanisms of SMOCs action in embryo developments and related diseases are summarized in Table 1.…”

Section: Smoc Functions In Cells and Embryo Developmentmentioning

confidence: 99%

Secreted modular calcium-binding proteins in pathophysiological processes and embryonic development

Gao

Mok

Zhuang

2019

Chinese Medical Journal

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Objective:Secreted modular calcium-binding proteins (SMOCs) are extracellular glycoproteins of the secreted protein, acidic, and rich in cysteine-related modular calcium-binding protein family and include two isoforms, SMOC1 and SMOC2, in humans. Functionally, SMOCs bind to calcium for various cell functions. In this review, we provided a summary of the most recent advancements in and findings of SMOC1 and SMOC2 in development, homeostasis, and disease states.Data sources:All publications in the PubMed database were searched and retrieved (up to July 24, 2019) using various combinations of keywords searching, including SMOC1, SMOC2, and diseases.Study selection:All original studies and review articles of SMOCs in human diseases and embryo development written in English were retrieved and included.Results:SMOC1 and SMOC2 regulate embryonic development, cell homeostasis, and disease pathophysiology. They play an important role in the regulation of cell cycle progression, cell attachment to the extracellular matrix, tissue fibrosis, calcification, angiogenesis, birth defects, and cancer development.Conclusions:SMOC1 and SMOC2 are critical regulators of many cell biological processes and potential therapeutic targets for the control of human cancers and birth defects.

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Section: Smoc Functions In Cells and Embryo Developmentmentioning

confidence: 99%

Secreted modular calcium-binding proteins in pathophysiological processes and embryonic development

Gao

Mok

Zhuang

2019

Chinese Medical Journal

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“…S1B). Based on these different phenotypes caused by altered BMP signaling, multiple evolutionarily conserved regulators of BMP signaling have been identified in C. elegans (18)(19)(20)(21)(22)(23)(24). Importantly, endocytosis and postendocytic trafficking of BMP receptors have also been found to be critical in regulating BMP signaling in C. elegans (7,25).…”

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confidence: 99%

Tetraspanins TSP-12 and TSP-14 function redundantly to regulate the trafficking of the type II BMP receptor in Caenorhabditis elegans

Liu

Shi

Nzessi

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Tetraspanins are a unique family of 4-pass transmembrane proteins that play important roles in a variety of cell biological processes. We have previously shown that 2 paralogous tetraspanins in Caenorhabditis elegans, TSP-12 and TSP-14, function redundantly to promote bone morphogenetic protein (BMP) signaling. The underlying molecular mechanisms, however, are not fully understood. In this study, we examined the expression and subcellular localization patterns of endogenously tagged TSP-12 and TSP-14 proteins. We found that TSP-12 and TSP-14 share overlapping expression patterns in multiple cell types, and that both proteins are localized on the cell surface and in various types of endosomes, including early, late, and recycling endosomes. Animals lacking both TSP-12 and TSP-14 exhibit reduced cell-surface levels of the BMP type II receptor DAF-4/BMPRII, along with impaired endosome morphology and mislocalization of DAF-4/BMPRII to late endosomes and lysosomes. These findings indicate that TSP-12 and TSP-14 are required for the recycling of DAF-4/BMPRII. Together with previous findings that the type I receptor SMA-6 is recycled via the retromer complex, our work demonstrates the involvement of distinct recycling pathways for the type I and type II BMP receptors and highlights the importance of tetraspanin-mediated intracellular trafficking in the regulation of BMP signaling in vivo. As TSP-12 and TSP-14 are conserved in mammals, our findings suggest that the mammalian TSP-12 and TSP-14 homologs may also function in regulating transmembrane protein recycling and BMP signaling.

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“…Thus it is of interest not only to study the various phenotypes corresponding to those modulators, but to use a variety of Sma/Mab phenotypes to look for new regulators. We already know that some of those associated proteins do not determine male tail formation (i.e., SMA-10 [ 5 ], and this study; DRAG-1 [ 4 ]; SMOC-1 [ 30 ]), but to our knowledge, no other phenotypes (apart from male tail, body size and mesoderm formation) are investigated in relation to those associated proteins.…”

Section: Discussionmentioning

confidence: 99%

SMA-10 Is a Non-Canonical Member of the TGF-β Sma/Mab Pathway and Immunity Regulator via the DAF-2 Insulin Receptor in Caenorhabditis elegans

Lucas

Jiménez

Sánchez-Pavón

et al. 2021

IJMS

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Transforming growth factor β (TGF-β) signalling pathways are highly conserved across metazoa and play essential roles not only during development but also in adult tissue maintenance. Alterations of these pathways usually result in a plethora of pathologies. In the nematode Caenorhabditis elegans, the TGF-β Sma/Mab (small/male abnormal) pathway regulates various worm phenotypes such as body size, immune response, ageing, matricide and reproductive span. SMA-10 has been described as a positive modulator of worm body size through the TGF-β Sma/Mab pathway. To better understand if SMA-10 is a core component of the pathway, we use gene epistatic analysis to assess the contribution of SMA-10 to various phenotypes regulated by TGF-β Sma/Mab. We confirm that SMA-10 controls body size and find that it also affects the matricide and reproductive span of the nematodes. However, neither male tail formation (previously reported) nor ageing appeared altered. Lastly, although null sma-10 worms are more susceptible to Pseudomonas aeruginosa infections than wild-types, this response does not depend on TGF-β Sma/Mab but on the insulin receptor DAF-2. We also show that the expression of sma-10 in either hypodermis or intestine fully rescues the wild-type immune response. Our results contribute to understanding the role of SMA-10 as a context-dependent component of TGF-β Sma/Mab, and reveal a function of SMA-10 in immunity in association to the Insulin/insulin-like growth factor signalling (IIS) pathway.

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The Caenorhabditis elegans SMOC-1 Protein Acts Cell Nonautonomously To Promote Bone Morphogenetic Protein Signaling

Cited by 11 publications

References 71 publications

Secreted modular calcium-binding proteins in pathophysiological processes and embryonic development

Secreted modular calcium-binding proteins in pathophysiological processes and embryonic development

Tetraspanins TSP-12 and TSP-14 function redundantly to regulate the trafficking of the type II BMP receptor in Caenorhabditis elegans

SMA-10 Is a Non-Canonical Member of the TGF-β Sma/Mab Pathway and Immunity Regulator via the DAF-2 Insulin Receptor in Caenorhabditis elegans

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