ZSWIM8 is a myogenic protein that partly prevents C2C12 differentiation

Okumura, Fumihiro; Oki, Nodoka; Fujiki, Yuha; Ikuta, Rio; Osaki, Kana; Hamada, Shun; Nakatsukasa, Kunio; Hisamoto, Naoki; Hara, Taichi; Kamura, Takumi

doi:10.1038/s41598-021-00306-6

Cited by 9 publications

(4 citation statements)

References 37 publications

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“…Surprisingly, we did not detect a difference in the localization between Pldo WT and Pldo ΔC in either wing cells (Figs 5E and S5C and D), or hemocytes (Fig S5B). Similar to Scar (Zallen et al, 2002;Kunda et al, 2003;Beli et al, 2008;Rodriguez-Mesa et al, 2012), Pldo localization is detected throughout the cell, which has also been noted for its human ortholog ZSWIM8 (Okumura et al, 2021).…”

Section: N-terminal Region Of Pldo Is Sufficient To Induce Filopodia ...supporting

confidence: 65%

The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization

et al. 2022

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Actin filament polymerization can be branched or linear, which depends on the associated regulatory proteins. Competition for actin monomers occurs between proteins that induce branched or linear actin polymerization. Cell specialization requires the regulation of actin filaments to allow the formation of cell type–specific structures, like cuticular hairs in Drosophila, formed by linear actin filaments. Here, we report the functional analysis of CG34401/pelado, a gene encoding a SWIM domain–containing protein, conserved throughout the animal kingdom, called ZSWIM8 in mammals. Mutant pelado epithelial cells display actin hair elongation defects. This phenotype is reversed by increasing actin monomer levels or by either pushing linear actin polymerization or reducing branched actin polymerization. Similarly, in hemocytes, Pelado is essential to induce filopodia, a linear actin-based structure. We further show that this function of Pelado/ZSWIM8 is conserved in human cells, where Pelado inhibits branched actin polymerization in a cell migration context. In summary, our data indicate that the function of Pelado/ZSWIM8 in regulating actin cytoskeletal dynamics is conserved, favoring linear actin polymerization at the expense of branched filaments.

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Section: N-terminal Region Of Pldo Is Sufficient To Induce Filopodia ...supporting

confidence: 65%

The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization

et al. 2022

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“…Figure S5B). Similar to Scar (Beli et al, 2008;Kunda et al, 2003;Rodriguez-Mesa et al, 2012;Zallen et al, 2002), Pldo localization is detected throughout the cell, which has also been noted for its human homologue ZSWIM8 (Okumura et al, 2021).…”

Section: N-terminal Region Of Pldo Is Sufficient To Induce Filopodia ...supporting

confidence: 64%

The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization

Pelayo

Olguı́n

Mlodzik

et al. 2022

Preprint

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Actin filament polymerization can be branched or linear, which depends on the associated regulatory proteins. Competition for Actin monomers occurs between proteins that induce branched or linear actin polymerization. Cell specialization requires the regulation of actin filaments to allow the formation of cell-type specific structures, like cuticular hairs in Drosophila, formed by linear actin filaments. Here, we report the functional analysis of CG34401/pelado, a gene encoding a SWIM domain containing protein, conserved throughout the animal kingdom. Mutant pelado epithelial cells display actin hair elongation defects. This phenotype is reversed by increasing Actin monomer levels or by either pushing linear actin polymerization or reducing branched actin polymerization. The same behavior occurs in hemocytes, where Pelado is essential to induce filopodia, a linear actin-based structure. We further show that this function of Pelado, ZSWIM8 in mammals, is conserved in human cells, where Pelado inhibits branched actin polymerization in a cell migration context. In summary, our data indicate that the function of Pelado/ZSWIM8 in regulating actin cytoskeletal dynamics is conserved, favoring linear actin polymerization at the expense of branched filaments.

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“…The extent to which phenotypes observed in these different animals arise from the loss of TDMD, rather than some other function of ZSWIM8, is still an open question. Indeed, ZSWIM8 is proposed to regulate neural development, myogenesis, and actin dynamics through mechanisms that do not involve TDMD (Wang et al, 2013, Wang et al, 2022, Okumura et al, 2021, Molina-Pelayo et al, 2022.…”

Section: Phenotypic Consequences Of Zswim8 Knockoutmentioning

confidence: 99%

ZSWIM8 destabilizes many murine microRNAs and is required for proper embryonic growth and development

et al. 2023

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MicroRNAs (miRNAs) pair to sites in mRNAs to direct the degradation of these RNA transcripts. Conversely, certain RNA transcripts can direct the degradation of particular miRNAs. This target-directed miRNA degradation (TDMD) requires the ZSWIM8 E3 ubiquitin ligase. Here, we report the function of ZSWIM8 in the mouse embryo.Zswim8–/– embryos were smaller than their littermates and died near the time of birth. This highly penetrant perinatal lethality was apparently caused by a lung sacculation defect attributed to failed maturation of alveolar epithelial cells. Some mutant individuals also had heart ventricular septal defects. These developmental abnormalities were accompanied by aberrant accumulation of >50 miRNAs observed across 12 tissues, which often led to enhanced repression of their mRNA targets. These ZSWIM8-sensitive miRNAs were preferentially produced from genomic miRNA clusters, and in some cases, ZSWIM8 caused a switch in the dominant strand or isoform that accumulated from a miRNA hairpin—observations suggesting that TDMD provides a mechanism to uncouple co-produced miRNAs from each other. Overall, our findings indicate that the regulatory influence of ZSWIM8, and presumably TDMD, in mammalian biology is widespread and consequential, and posit the existence of many yet-unidentified transcripts that trigger miRNA degradation.

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ZSWIM8 is a myogenic protein that partly prevents C2C12 differentiation

Cited by 9 publications

References 37 publications

The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization

The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization

The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization

ZSWIM8 destabilizes many murine microRNAs and is required for proper embryonic growth and development

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