更新于：2024-11-01

FHOD1

更新于：2024-11-01

基本信息

别名

FH1/FH2 domain-containing protein 1、FHOD1、FHOS

+ [4]

简介

Required for the assembly of F-actin structures, such as stress fibers. Depends on the Rho-ROCK cascade for its activity. Contributes to the coordination of microtubules with actin fibers and plays a role in cell elongation. Acts synergistically with ROCK1 to promote SRC-dependent non-apoptotic plasma membrane blebbing.

关联

100 项与 FHOD1 相关的临床结果

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100 项与 FHOD1 相关的转化医学

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0 项与 FHOD1 相关的专利（医药）

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133

项与 FHOD1 相关的文献（医药）

2024-11-01·Molecular Biology of the Cell

FHOD-1 and profilin protect sarcomeres against contraction-induced deformation> in C. elegans

Article

作者: Geary, Meaghan A. ; Littlefield, Ryan S. ; Pruyne, David ; Lesanpezeshki, Leila ; Kimmich, Michael J. ; Yingling, Curtis V. ; Sundaramurthy, Sumana ; Vanapalli, Siva A.

Formin HOmology Domain 2-containing (FHOD) proteins are a subfamily of actin-organizing formins important for striated muscle development in many animals. We showed previously that absence of the sole FHOD protein, FHOD-1, from Caenorhabditis elegans results in thin body wall muscles with misshapen dense bodies that serve as sarcomere Z-lines. We demonstrate here that mutations predicted to specifically disrupt actin polymerization by FHOD-1 similarly disrupt muscle development, and that FHOD-1 cooperates with profilin PFN-3 for dense body morphogenesis, and with profilins PFN-2 and PFN-3 to promote body wall muscle growth. We further demonstrate that dense bodies in worms lacking FHOD-1 or PFN-2/PFN-3 are less stable than in wild-type animals, having a higher proportion of dynamic protein, and becoming distorted by prolonged muscle contraction. We also observe accumulation of actin and actin depolymerization factor/cofilin homologue UNC-60B in body wall muscle of these mutants. Such accumulations may indicate targeted disassembly of thin filaments dislodged from unstable dense bodies, possibly accounting for the abnormally slow growth and reduced body wall muscle strength in fhod-1 mutants. Overall, these results implicate FHOD protein–mediated actin assembly in forming stable sarcomere Z-lines, and identify profilin as a new contributor to FHOD activity in striated muscle development.

2024-10-01·Journal of Biological Chemistry

Methylation and phosphorylation of formin homology domain proteins (Fhod1 and Fhod3) by protein arginine methyltransferase 7 (PRMT7) and Rho Kinase (ROCK1)

Article

作者: Valencia, Dylan A ; Lowe, Troy L. ; Velasquez, Vicente E ; Velasquez, Vicente E. ; Quinlan, Margot E ; Quinlan, Margot E. ; Clarke, Steven G. ; Valencia, Dylan A. ; Clarke, Steven G ; Lowe, Troy L

Protein post translational modifications (PTMs) can regulate biological processes by altering an amino acid's bulkiness, charge, and hydrogen bonding interactions. Common modifications include phosphorylation, methylation, acetylation and ubiquitylation. Although a primary focus of studying PTMs is understanding the effects of a single amino acid modification, the possibility of additional modifications increases the complexity. For example, substrate recognition motifs for arginine methyltransferases and some serine/threonine kinases overlap, leading to potential enzymatic crosstalk. In this study we have shown that the human family of formin homology domain containing proteins (Fhods) contain a substrate recognition motif specific for human protein arginine methyltransferase 7 (PRMT7). In particular, PRMT7 methylates two arginine residues in the diaphanous autoinhibitory domain (DAD) of the family of Fhod proteins: R1588 and/or R1590 of Fhod3 isoform 4. Additionally, we confirmed that S1589 and S1595 in the DAD domain of Fhod3 can be phosphorylated by Rho/ROCK1 kinase. Significantly, we have determined that if S1589 is phosphorylated then PRMT7 cannot subsequently methylate R1588 or R1590. In contrast, if R1588 or R1590 of Fhod3 is methylated then ROCK1 phosphorylation activity is only slightly affected. Finally, we show that the interaction of the N-terminal DID domain can also inhibit the methylation of the DAD domain. Taken together these results suggest that the family of Fhod proteins, potential in vivo substrates for PRMT7, might be regulated by a combination of methylation and phosphorylation.

2024-04-01·Science of The Total Environment

Reprogramming of DNA methylation patterns mediates perfluorooctane sulfonate-induced fetal cardiac dysplasia

Article

作者: Nie, Zhiqiang ; Qiu, Min ; Zhuang, Jian ; Dong, Guanghui ; Shi, Yan ; Liu, Mingqin ; Ou, Yanqiu ; Li, Xiaohong ; Chen, Jing ; Chen, Jimei

Prenatal exposure to perfluorooctane sulfonate (PFOS) is associated with adverse health effects, including congenital heart disease, yet the underlying mechanisms remain elusive. Herein, we aimed to evaluate the embryotoxicity of PFOS using C57BL/6 J mice to characterize fetal heart defects after PFOS exposure, with the induction of human embryonic stem cells (hESC) into cardiomyocytes (CMs) as a model of early-stage heart development. We also performed DNA methylation analysis to clarify potential underlying mechanisms and identify targets of PFOS. Our results revealed that PFOS caused septal defects and excessive ventricular trabeculation cardiomyopathy at 5 mg/kg/day in embryonic mice and inhibited the proliferation and pluripotency of ESCs at concentrations >20 μM. Moreover, it decreased the beating rate and the population of CMs during cardiac differentiation. Decreases were observed in the abundances of NPPA+ trabecular and HEY2+ compact CMs. Additionally, DNA methyl transferases and ten-eleven translocation (TET) dioxygenases were regulated dynamically by PFOS, with TETs inhibitor treatment inducing significant decreases similar as PFOS. 850 K DNA methylation analysis combined with expression analysis revealed several potential targets of PFOS, including SORBS2, FHOD1, SLIT2, SLIT3, ADCY9, and HDAC9. In conclusion, PFOS may reprogram DNA methylation, especially demethylation, to induce cardiac toxicity, causing ventricular defects in vivo and abnormal cardiac differentiation in vitro.