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Matsunaga, K.

Publications and source records attributed to Matsunaga, K..

8 recordsLinked to original sources

Lac1-dependent ceramide synthesis couples septum assembly to cell separation in Schizosaccharomyces pombe

Ceramides are precursors of complex sphingolipids and bioactive membrane lipids. In the fission yeast Schizosaccharomyces pombe, they are produced by a ceramide synthase with two catalytic subunits, Lac1 and Lag1, which are redundant but not functionally equivalent: only Lac1 is required for normal growth and cell size. Why Lac1 has this unique role, and how ceramide synthesis contributes to cell morphogenesis, remain unknown. Here, we show that Lac1 couples septum assembly to cell separation. Cells lacking Lac1 die predominantly during cell separation and build septa with a thinner primary layer and markedly thicker secondary layers, accompanied by altered deposition of {beta}-(1,3)-glucans and galactomannan. These defects are not rescued by osmotic stabilization. The essential glucan synthase Bgs4 is mislocalized to cytoplasmic granules, and total {beta}-(1,3)-glucan synthase activity is partially reduced. Nevertheless, Ags1, Bgs1 and Bgs4 accumulate to higher levels and persist almost twice as long at the division site, indicating defective clearance rather than delivery of the septum-synthesis machinery. Plasma membrane sterol distribution remains unaffected. To accurately impair ceramide synthesis, we isolated thermosensitive lac1-ts alleles in a lag1{Delta} background. Their substitutions cluster in the conserved TRAM/LAG1 domain. Metabolic labeling showed that these alleles reduce ceramide synthesis at the restrictive temperature. Molecular dynamics simulations indicated that two substitutions perturb distinct contacts with C26-CoA, while Lac1-M167T loses its endoplasmic reticulum localization. Acute inactivation recapitulates the deletion phenotype, causing septum accumulation and cell death. Together, our findings establish that Lac1-dependent ceramide synthesis is required for the orderly completion of septum assembly and cell separation.

cell biology↗

The revised three-step detour pathway in dolichol biosynthesis is evolutionarily conserved in budding yeast

The identification of SRD5A3, a causative gene for congenital disorders of glycosylation (CDGs), together with its yeast ortholog DFG10, established the prevailing model that dolichol is synthesized from polyprenol in a single step. Subsequently, a recent discovery of DHRSX in CDG patients revised this view and led to the proposal of a three-step detour pathway for dolichol biosynthesis. However, it remains unclear whether this pathway represents a conserved mechanism or reflects evolutionary diversity in eukaryotes. Here, we identified TDA5 as a yeast ortholog of DHRSX. Deletion of TDA5 caused glycosylation defects, reduced dolichol levels, and accumulated polyprenol. All these phenotypes were rescued by expression of DHRSX, but not by DFG10 or SRD5A3. These findings show that Tda5 serves the same function as DHRSX in yeast, thereby demonstrating conservation of the three-step detour pathway in yeast and supporting a broader eukaryotic framework for dolichol biosynthesis.

cell biology↗

GPI lipid remodeling regulates lipophagy by forming lipid domains in response to glucose deprivation

Lipophagy is an important microautophagic process that degrades lipid droplets (LDs) to mobilize stored lipids as an energy source during nutrient starvation. However, the molecular mechanisms regulating lipophagy in response to nutrient starvation remain poorly understood. We found that budding yeast mutants defective in glycosylphosphatidylinositol (GPI) lipid remodeling exhibited aberrant accumulation of lipid droplets (LDs) and neutral lipids under glucose starvation. Our data suggest that the accumulation results from a failure of vacuolar liquid-ordered (Lo) domain-mediated lipophagy. Furthermore, we demonstrated that glycosylphosphatidylinositol-anchored proteins (GPI-APs) localize to vacuoles in response to glucose depletion and that a mutant defective in endocytosis has defects in both vacuolar Lo domain formation and lipophagy. These results imply that GPI lipid remodeling is required for Lo domain-mediated lipophagy upon glucose starvation. We propose that endocytosis functions to supply the lipid portion of GPI-APs, remodeled to C26 diacylglycerol, to the vacuolar membrane for Lo domain formation. Summary StatementOur data suggest that the endocytic transport of GPI-APs remodeled with C26 diacylglycerol to the vacuole is required for vacuolar Lo domain formation and subsequent lipophagy in response to glucose deprivation. This reveals the essential role of GPI lipid remodeling in ensuring lipophagy to adapt to changes in nutrient availability.

cell biology↗

Interoceptive Accuracy Modulates Electroencephalogram During Music Recall Tasks

The ability to perceive and recall music varies with individuals, depending on musical experience, age, and emotional memory. Emotional memory processing occurs in the insular cortex, which is also implicated in interoception, the perception of internal bodily states, suggesting a potential link to music recall. However, the direct relationship between interoception and music recall remains largely unexplored. We hypothesize that individual differences in music recall are influenced by interoceptive accuracy. To test this, we conducted an electroencephalogram (EEG) experiment where participants listened to and recalled both familiar and unfamiliar music. Participants interoceptive accuracy was assessed through a heartbeat counting task. We observed greater alpha power suppression during recall periods in familiar music than in unfamiliar music. Furthermore, participants with higher interoceptive accuracy exhibited stronger alpha power suppression during music recall. These findings suggest that music recall involves interoceptive attention. Considering the insular cortexs role in both interoception and emotional memory, it may play a critical role in the neural processes underlying music recall, which should be further investigated.

neuroscience↗

Species distribution modeling for conservation science: new predictor layers, reproducible code, and an evaluation of California protected areas

AimOur study provides foundational resources for future SDMing: methods for generating fine-scale, equal-area predictor datasets and best-practice SDM guidelines. We also provide reproducible code to streamline their implementation. LocationSouthwestern North America MethodsUsing over 215,000 research-grade iNaturalist occurrence records for 127 species of conservation concern or scientific interest in California and surrounding area, we quantified and compared SDM performance between two predictor datasets that differ in their source of bioclimatic data, spatial resolution, and coordinate reference system: one generated using ClimateNA software (resolution = 300 x 300 m; NAD83/California Albers) and the other using existing WorldClim data (varying resolution = [~]669-797 x 926 m; WGS84). We also compared two modeling algorithms (MaxEnt vs Random Forests), and two background point selection strategies (random points vs weighted points accounting for sampling effort). As an example application, we used SDM predictions to evaluate the conservation value of different protected area types within California. ResultsClimateNA outperformed WorldClim for 94% of species, Random Forests outperformed MaxEnt for 87%, and random background points outperformed weighted background points for 100%. All differences were statistically significant. Together, the ClimateNA dataset, Random Forests, and random background points achieved highest performance for 86% of species. Using this best-performing set of models, we found that regional parks, county parks, state beaches, and open spaces in California were highest in multi-species suitability, while larger protected areas, such as national parks and national forests, generally exhibited surprisingly low suitability. Substantial spatial biases intrinsic to SDMing with unprojected predictor datasets (e.g., WGS84) are described, along with clear solutions using equal-area predictor datasets. Main conclusionsConsiderable disparity was observed among the performance of common SDM methods. This study highlights the importance of fine-scale, equal-area predictor datasets and best-practice guidelines, and demonstrates how SDMs can provide critical insights into protected area planning.

ecology↗

Effect of predicting familiar melodies on alpha power

The processing of music and language share similar characteristics. Previous studies indicated that the similarity between language and melody was observed in event-related potentials to the deviation of a word and tone, respectively. We focused on a language study that demonstrated strong suppression of the alpha power in the presence of easily predictable words. Motivated by the physiological similarity between language and music, this study hypothesized that predictable music might suppress the alpha power. We measured electroencephalogram (EEG) signals while a melody followed by silence was presented for a participant who imagined the melody during the silent part of the music. The participants scored the melodys familiarity to quantify the ease of prediction and imagination. We observed similarity to language processing. For familiar melodies, alpha power suppression was observed in the left frontal and left central regions. Further, we observed Bereitschaftspotential (a negative slope) in both familiar and unfamiliar conditions before the silent interval. Moreover, a network analysis revealed that information flow from the right sensory-motor cortex to the right auditory cortex in the beta band was stronger for familiar music than for unfamiliar music. Considering the previous findings that motor preparation and execution suppress the alpha power in the left frontal and left central regions, the alpha band suppression under music prediction suggests a motor interaction during music processing in the prediction of melodies.

neuroscience↗

Functional hierarchy among different Rab27 effectors involved in secretory granule exocytosis

The Rab27 effectors play versatile roles in regulated exocytosis. In pancreatic beta cells, exophilin-8 anchors granules in the peripheral actin cortex, whereas granuphilin and melanophilin mediate granule fusion with and without stable docking to the plasma membrane, respectively. However, it is unknown whether these coexisting effectors function in parallel or in sequence to support the whole insulin secretory process. Here, we investigate their functional relationship by comparing the exocytic phenotypes in beta cells simultaneously lacking two effectors with those lacking one of them. Analyses of prefusion profiles by total internal reflection fluorescence microscopy indicate that melanophilin exclusively functions downstream of exophilin-8 to mobilize granules for fusion from the actin network to the plasma membrane after stimulation. The two effectors are physically linked via the exocyst complex. Downregulation of the exocyst component affects granule exocytosis only in the presence of exophilin-8. Exophilin-8 also promotes fusion of granules stably docked to the plasma membrane mediated by granuphilin, although it is dispensable for granule residence beneath the plasma membrane. The current study presents the first diagram for multiple intracellular paths of granule exocytosis and for functional hierarchy among different Rab27 effectors in the same cell.

cell biology↗

Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis

There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from saliva on the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques. We investigated the general and oral conditions from each patient and performed next-generation sequencing analysis for all bacterial samples. There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the saliva were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that in saliva present on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. These results indicated that oral bacteria did not affect the formation of atheromatous plaques directly. However, the metabolic products of microbiome or the host inflammatory response might indirectly influence the composition of atheromatous plaques.

microbiology↗