This study reveals that PRMT1 regulates the interaction between SCYL1 and γ₂-COP for Golgi organization via SCYL1 arginine methylation. We propose that SCYL1 arginine methylation by PRMT1 contributes to axon and dendrite morphogenesis in neurons. This report contributes to the elucidation of brain development via arginine methylation.

Highly specialized glial cells wrap axons with a multilayered myelin membrane in vertebrates. Myelin serves essential roles in the functioning of the nervous system. Axonal degeneration is the major cause of permanent neurological disability in primary myelin diseases. Many glycoproteins have been identified in myelin, and a lack of one myelin glycoprotein results in abnormal myelin structures in many cases. However, the roles of glycans on myelin glycoproteins remain poorly understood. Here, we report that sulfatedN-glycans are involved in peripheral nervous system (PNS) myelination. PNS myelin glycoproteins contain highly abundant sulfatedN-glycans. Major sulfatedN-glycans were identified in both porcine and mouse PNS myelin, demonstrating that the 6-O-sulfation ofN-acetylglucosamine (GlcNAc-6-O-sulfation) is highly conserved in PNS myelin between these species. P₀protein, the most abundant glycoprotein in PNS myelin and mutations in which at the glycosylation site cause Charcot-Marie-Tooth neuropathy, has abundant GlcNAc-6-O-sulfatedN-glycans. Mice deficient inN-acetylglucosamine-6-O-sulfotransferase-1 (GlcNAc6ST-1) failed to synthesize sulfatedN-glycans and exhibited abnormal myelination and axonal degeneration in the PNS. Taken together, this study demonstrates that GlcNAc6ST-1 modulates PNS myelination and myelinated axonal survival through the GlcNAc-6-O-sulfation ofN-glycans on glycoproteins. These findings may provide novel insights into the pathogenesis of peripheral neuropathy.

The proteasome is essential for cellular responses to various physiological stressors. However, how proteasome function impacts the stress resilience of regenerative damaged motor neurons remains unclear. Here, we develop a unique mouse model using a regulatory element of the activating transcription factor (Atf3) gene to label mitochondria in a damage‐induced manner while simultaneously genetically disrupting the proteasome. Using this model, we observed that in injury‐induced proteasome‐deficient mouse motor neurons, the increase of mitochondrial influx from soma into axons is inhibited because neurons fail to disassemble ankyrin G, an organizer of the axon initial segment (AIS), in a proteasome‐dependent manner. Further, these motor neurons exhibit amyotrophic lateral sclerosis (ALS)‐like degeneration despite having regenerative potential. Selectively vulnerable motor neurons in SOD1^G93A ALS mice, which induce ATF3 in response to pathological damage, also fail to disrupt the AIS, limiting the number of axonal mitochondria at a pre‐symptomatic stage. Thus, damage‐induced proteasome‐sensitive AIS disassembly could be a critical post‐translational response for damaged motor neurons to temporarily transit to an immature state and meet energy demands for axon regeneration or preservation.

Individual taste sensitivity influences food preferences, nutritional control, and health, and differs greatly between individuals. The purpose of this study was to establish a method of measuring and quantifying an individual’s taste sensitivity and to evaluate the relationship between taste variation and genetic polymorphisms in humans using agonist specificities of the bitter taste receptor gene, TAS2R38, with the bitter compound 6-n-propylthiouracil (PROP). We precisely detected the threshold of PROP bitter perception by conducting the modified two-alternative forced-choice (2AFC) procedure with the Bayesian staircase procedure of the QUEST method and examined genetic variation in TAS2R38 in a Japanese population. There were significant differences in PROP threshold between the three TAS2R38 genotype pairs for 79 subjects: PAV/PAV vs AVI/AVI, p < 0.001; PAV/AVI vs AVI/AVI, p < 0.001; and PAV/PAV vs PAV/AVI, p < 0.01. Our results quantified individual bitter perception as QUEST threshold values: the PROP bitter perception of individuals with the PAV/PAV or PAV/AVI genotypes was tens to fifty times more sensitive than that of an individual with the AVI/AVI genotype. Our analyses provide a basic model for the accurate estimation of taste thresholds using the modified 2AFC with the QUEST approach.