Biology subjects

Akimoto, Y.

Publications and source records attributed to Akimoto, Y..

4 recordsLinked to original sources

bioRxiv2025

Impairment in axonal translation and cytoplasmic viscosity during aging in sensory neurons

Mitochondria are trafficked along axons and provide the energy required for several intracellular mechanisms including molecular transport and local translation, which is believed to contribute to the homeostasis of the axonal compartment. Decline in mitochondria activity is one of the hallmarks of aging. It is still unclear, though, whether this decline corresponds to a concomitant reduction in the extent of axonal translation during aging. Using live cell imaging of sensory neurons, we found a significant decrease in the number of active mitochondria and the percentage of mitochondria localized to axons in aged mice compared to young mice. This decrease was mirrored by a loss of intracellular ATP as well as an ATP-dependent decrease in axoplasmic viscosity. In addition, the size of G3BP1 positive axonal granules and the number of FMRP axonal granules increased. Cumulatively, we found a functional decrease in the overall level of axonal translation in aged neurons. We were able to rescue this effect by increasing ATP synthesis, which induced a global decrease in axoplasmic viscosity, while promoting RNA granule solubilization and boosting axonal translation. Proteomic analysis of newly synthesized proteins in axons of aged vs young neurons revealed a dysregulation of pathways related to axonal biology and growth. We identified MAP1B and STAT3 as proteins whose axonal local synthesis was impaired in aged axons, and more notably show that this impairment could be rescued by increasing ATP synthesis. We believe that this research sheds light on axonal translation in aged neurons and its relationship with energy sources inside the axonal compartment, possibly presenting an opportunity for future therapeutics.

neuroscience↗

bioRxiv2025

PU.1 and TGF-β signaling transactivate CD103 expression in mast cells and dendritic cells: Opposite roles of GATA2 in the expression of mucosal mast cell-specific genes

Mucosal mast cells (MMCs) are distinguished from connective tissue MCs by the specific expression of integrin CD103 (E/{beta}7) and MC proteases Mcpt1 and Mcpt2. Although the expression of the Mcpt1 and Mcpt2 genes is cooperatively regulated by the transcription factor GATA2 and TGF-{beta} signaling in MMCs, the transcriptional mechanism of CD103 expression remains unknown. Here, we found that surface CD103 and Itgae mRNA levels were significantly increased by the knockdown (KD) of Gata2 in bone marrow-derived MCs (BMMCs), which was accelerated by a TGF-{beta} stimulation. Since the mRNA levels of Spi1 (encoding PU.1) were increased in Gata2 KD BMMCs, we examined the effects of PU.1 on CD103 expression. As expected, CD103 levels on BMMCs were significantly decreased by Spi1 KD and increased by Spi1 overexpression. Spi1 KD suppressed Itgae expression even in the presence of TGF-{beta} in BMMCs and peritoneal MCs, whereas Gata2 KD amplified the TGF-{beta}-induced increase in Itgae expression. The amount of PU.1 binding to the cis-element in the Itgae gene was significantly and moderately increased by Gata2 KD and the TGF-{beta} stimulation, respectively. Since PU.1 is an essential transcription factor for dendritic cells (DCs), we examined the role of PU.1 in CD103 expression on DCs. The KD experiment using BMDCs showed a significant decrease in CD103 levels in Spi1 siRNA-transfected BMDCs. We concluded that PU.1 affected CD103 expression on MMCs and DCs by transactivating the Itgae gene, and also that GATA2, which positively regulated the MMC-specific expression of Mcpt1 and 2, inhibited CD103 expression by repressing PU.1.

molecular biology↗

bioRxiv2023

Nuclear cytoophidia assembly represses transcriptional activity to control skeletal development and homeostasis

Compartmentation via filamentation is an evolutionarily conserved subcellular structure that fine-tunes the inherent activity of proteins. Cytoophidia represent a typical class of filamentous structures controlling enzymatic activities. Despite eukaryotic cells containing both cytoplasmic cytoophidia and nuclear cytoophidia, the physiological significance of nuclear cytoophidia is largely unknown. Here we show that nuclear filamentation inhibits the transcriptional activity of Impdh2 required for limb formation and bone resorption. Impdh2 deletion in mouse limb mesenchymal progenitors causes severe skeletal dysplasia by impairing endochondral ossification and chondrocyte differentiation. Additionally, Impdh2 deficiency in myeloid lineages leads to an increased bone mass via impeding osteoclast differentiation. Furthermore, Impdh2 regulates osteoclastic mitochondrial biogenesis and function. We propose that the nuclear compartmentalization of Impdh2 regulates the transcriptional activity during skeletal development and homeostasis.

cell biology↗

bioRxiv2023

Endothelial tissue remodeling induced by intraluminal pressure enhances paracellular solute transport

The endothelial layers of the microvasculature regulate the transport of solutes to the surrounding tissues. It remains unclear how this barrier function is affected by blood flow-induced intraluminal pressure. Using a 3D microvessel model, we compare the transport of macromolecules through endothelial tissues at mechanical rest or with intraluminal pressure, and correlate these data with electron microscopy of endothelial junctions. Upon application of an intraluminal pressure of 100 Pa, we demonstrate that the flow through the tissue increases by 135%. This increase is associated with a 25% expansion of microvessel diameter, which leads to tissue remodeling and thinning of the paracellular junctions. We recapitulate these data with the deformable monopore model, in which the increase in paracellular transport is explained by the augmentation of the diffusion rate across thinned junctions under mechanical stress. We therefore suggest that the deformation of microvasculatures contributes to regulate their barrier function.

biophysics↗