Biology subjects

Komatsu, Y.

Publications and source records attributed to Komatsu, Y..

6 recordsLinked to original sources

bioRxiv2026

Aberrant ciliogenesis induced by enhanced BMP signaling causes heterotopic ossification

Bone morphogenetic protein (BMP) signaling is a principal driver of heterotopic ossification (HO), yet how aberrant BMP activity structurally reprograms cellular signaling machinery to develop HO remains unclear. Here, we identify BMP signaling as a direct upstream regulator of ciliogenesis that coordinates a multi-stage, pro-osteochondrogenic signaling relay during HO. Using a conditional gain-of-function BMP mouse model (Acvr1Q207D/+), we demonstrate that enhanced BMP signaling promotes primary cilium biogenesis and axonemal elongation through canonical Smad1/5/9-dependent transcriptional activation of intraflagellar transport (IFT) Ift20, a core component of the IFT machinery. Rather than operating via a singular downstream cascade, these elongated cilia establish a sensitized signaling hub. Genetic disruption of ciliary Hedgehog (Hh) transduction via Smoothened (Smo) deletion reveals that ciliary Hh signaling is dispensable for initial tissue condemnation but required for the subsequent proliferative expansion and maturation of HO. Conversely, complete genetic ablation of the ciliary structure via Ift20 deletion, or early pharmacological inhibition of ciliogenesis, significantly attenuates HO. Notably, this BMP-IFT20-cilia axis is functionally conserved within injury-responsive, PDGFR-positive fibro-adipogenic progenitor (FAP) populations harboring the clinically authentic Acvr1R206H/+ mutation responsible for fibrodysplasia ossificans progressiva (FOP) in mice. Together, these findings reveal that BMP signaling drives HO by structurally expanding the primary cilium, establishing a novel mechanism for HO development. SignificanceGrowth factor signaling instructs cellular behavior during tissue regeneration, but how they regulate cellular organelles to induce pathological fates remains poorly understood. This study reveals that Bone Morphogenetic Protein (BMP) signaling functions as a direct architectural regulator of the primary cilium, a critical cellular antenna. We show that BMP signaling directly transactivates intraflagellar transport machinery to structurally elongate the cilium, creating a sensitized signaling hub that drives heterotopic ossification. Our findings introduce a novel BMP-driven organelle regulation mechanism and establish a targetable cellular vulnerability to mitigate ectopic bone formation.

developmental biology↗

bioRxiv2025

Phosphorylation-Coupled Autoregulation Maintains Functional ER Exit Sites

Secretory proteins are synthesized in the endoplasmic reticulum (ER) and begin their transport from specialized domains on the ER called ER exit sites (ERES). We previously demonstrated that the interaction between TANGO1 and Sec16 is critical for ERES formation. In this study, we reveal that the phosphorylation of TANGO1 and Sec16 is regulated by a FAM83A/CK1-mediated negative feedback loop. Conversely, their dephosphorylation is regulated in a spatially distinct manner by different phosphatase complexes: PPP6R3/PPP6C for Sec16 and PPP1R15B/PPP1C for TANGO1. Excessive phosphorylation of either TANGO1 or Sec16 leads to ERES disassembly, while excessive dephosphorylation impairs secretion. Our findings demonstrate that maintaining a balanced phosphorylation state of TANGO1 and Sec16 through autoregulation by FAM83A/CK1 and the phosphatases PP1 and PP6 is essential for sustaining proper secretory activity at the ERES.

cell biology↗

bioRxiv2024

Remote Detection of Red-Edge Spectral Characteristics in Floating Aquatic Vegetation

The vegetation red-edge of terrestrial plants is a key biosignature for detecting Earth-like habitable exoplanets. Although water is essential for plants, an excess of water can limit the distribution of terrestrial vegetation. On planets with extensive water coverage and limited land, floating vegetation on the waters surface could serve as a crucial indicator of life. This study examined the spectral reflectance of floating plants across various scales, from individual leaves to lake-wide vegetation coverage. Our comparisons between individual leaves revealed that the red-edge of floating plants was equivalent to or even more pronounced than that of terrestrial plants. Although water can reduce plant reflectance, the naturally low reflectance of water enhances the detection sensitivity for floating vegetation. Seasonal changes, such as the proliferation of floating plants in summer and their decline in winter, lead to significant variations in lake reflectance. By analyzing satellite images of lakes and marshes over a five-year period, we confirmed that these seasonal variations in reflectance reliably indicate the presence of floating vegetation. The seasonal signal showed robustness to the effects of clouds, which pose another challenge on water-rich planets. We propose that floating vegetation be considered alongside, or even in place of, terrestrial vegetation in the search for extraterrestrial life.

plant biology↗

bioRxiv2024

A Novel Method to Visualize Active Small GTPases Unveils Distinct Sites of Sar1 Activation During Collagen Secretion.

Small GTPases are essential in various cellular signaling pathways, and detecting their activation within living cells is crucial for understanding cellular processes. Fluorescence resonance energy transfer is widely used to study the interaction between activated small GTPases and their effectors, but it is limited to those with well-defined effectors, excluding Sar1. Here, we present a novel method, SAIYAN (Small GTPase ActIvitY ANalyzing), for detecting the activation of endogenous small GTPases via fluorescent signals utilizing a split mNeonGreen system. We demonstrated Sar1 activation at the endoplasmic reticulum (ER) exit site and successfully detected its activation state in various cellular conditions. Utilizing the SAIYAN system in collagen-secreting cells, we discovered activated Sar1 localized both at ER exit sites and ER-Golgi intermediate compartment (ERGIC) regions. Additionally, impaired collagen secretion led to the confinement of activated Sar1 at the ER exit sites, underscoring the significance of Sar1 activation through the ERGIC in collagen secretion.

cell biology↗

bioRxiv2021

IFT20 is critical for early chondrogenesis during endochondral ossification

Ciliogenic components, such as the family of intraflagellar transport (IFT) proteins, are recognized to play key roles in endochondral ossification, a critical process to form most bones. However, it remains unclear how each IFT protein performs its unique function to regulate endochondral ossification. Here, we show that intraflagellar transport 20 (IFT20) is required for early chondrogenesis. Utilizing three osteo-chondrocyte lineage-specific Cre mice (Prx1-Cre, Col2-Cre and Aggrecan-CreERT2), we deleted Ift20 to examine its function. While chondrocyte-specific Ift20 deletion with Col2-Cre or Aggrecan-CreERT2 drivers did not cause overt skeletal defects, mesoderm-specific Ift20 deletion using Prx1-Cre (Ift20:Prx1-Cre) resulted in shortened limb outgrowth. Although primary cilia were not formed in Ift20:Prx1-Cre mice, ciliary Hedgehog signaling was only moderately affected. Interestingly, loss of Ift20 lead to upregulation of Fgf18 expression resulting in ERK1/2 activation and sustained Sox9 expression, thus preventing endochondral ossification. Inhibition of enhanced phospho-ERK1/2 activation partially rescued defective chondrogenesis in Ift20 mutant cells, supporting an important role for FGF signaling. Our findings demonstrate a novel mechanism of IFT20 in early chondrogenesis during endochondral ossification.

developmental biology↗

bioRxiv2019

Mitotic ER exit site dissociation is mediated by TANGO1 phosphorylation with CK1.

Golgi fragmentation and ER exit site dissociation are considered as the leading causes of mitotic block of secretion from the ER. Although the mechanisms of Golgi fragmentation have been extensively characterized, ER exit block early in mitosis is not well-understood. We previously found that TANGO1 organizes ER exit sites by directly interacting with Sec16. Here, we showed that TANGO1 is phosphorylated by casein kinase 1 (CK1) during mitosis. Interestingly, the interaction with Sec16 was abrogated by phosphorylation of TANGO1, leading to dissociation of the ER exit sites. Moreover, a TANGO1 mutant deficient in phosphorylation inhibited the mitotic dissociation of ER exit sites. In contrast, a TANGO1 mutant mimicking CK1-mediated phosphorylation dissociated ER exit sites in interphase cells. Although CK1 activity remains constant throughout the cell cycle, PP1, a phosphatase for which activity decreases during mitosis, participates in the regulation of TANGO1 phosphorylation. This is the first report demonstrating the mechanisms of ER exit site dissociation during mitosis.

cell biology↗