Systemic administrations of protamine heal subacute spinal cord injury in mice.

Spinal cord injury (SCI) results in damage to neural circuits that cause long-term locomotor and sensory disability. The objective of the present study is to evaluate whether a clinical drug, protamine, can be employed as a therapeutic agent for SCI. First, we examined the rescue effect of protamine on dystrophic endballs (DEs) cultured on a chondroitin sulfate (CS) gradient coating.

Functions of mucosal associated invariant T cells in eye diseases.

Mucosal-associated invariant T (MAIT) cells are a unique subset of T cells that recognizes metabolites derived from the vitamin B2 biosynthetic pathway. Since the identification of cognate antigens for MAIT cells, knowledge of the functions of MAIT cells in cancer, autoimmunity, and infectious diseases has been rapidly expanding. Recently, MAIT cells have been found to contribute to visual protection against autoimmunity in the eye.

Corrigendum: Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance.

[This corrects the article DOI: 10.3389/fimmu.2022.

PDZD8-deficient mice manifest behavioral abnormalities related to emotion, cognition, and adaptation due to dyslipidemia in the brain.

Although dyslipidemia in the brain has been implicated in neurodegenerative disorders, the molecular mechanisms underlying its pathogenesis have been largely unclear. PDZD8 is a lipid transfer protein and mice deficient in PDZD8 (PDZD8-KO mice) manifest abnormal accumulation of cholesteryl esters (CEs) in the brain due to impaired lipophagy, the degradation system of lipid droplets. Here we show the detailed mechanism of PDZD8-dependent lipophagy.

PDZD8-deficient mice accumulate cholesteryl esters in the brain as a result of impaired lipophagy.

Dyslipidemia including the accumulation of cholesteryl esters (CEs) in the brain is associated with neurological disorders, although the underlying mechanism has been unclear. PDZD8, a Rab7 effector protein, transfers lipids between endoplasmic reticulum (ER) and Rab7-positive organelles and thereby promotes endolysosome maturation and contributes to the maintenance of neuronal integrity. Here we show that CEs accumulate in the brain of PDZD8-deficient mice as a result of impaired lipophagy.

Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance.

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors.

Identifying Hyperreflective Foci in Diabetic Retinopathy via VEGF-Induced Local Self-Renewal of CX3CR1+ Vitreous Resident Macrophages.

Intraretinal hyperreflective foci (HRF) are significant biomarkers for diabetic macular edema. However, HRF at the vitreoretinal interface (VRI) have not been examined in diabetic retinopathy (DR). A prospective observational clinical study with 162 consecutive eyes using OCT imaging showed significantly increased HRF at the VRI during DR progression (P < 0.

Protrudin regulates FAK activation, endothelial cell migration and angiogenesis.

During angiogenesis, endothelial cells form protrusive sprouts and migrate towards the angiogenic stimulus. In this study, we investigate the role of the endoplasmic reticulum (ER)-anchored protein, Protrudin, in endothelial cell protrusion, migration and angiogenesis. Our results demonstrate that Protrudin regulates angiogenic tube formation in primary endothelial cells, Human umbilical vein endothelial cells (HUVECs).

Molecular machinery regulating organelle dynamics during axon growth and guidance.

Axon growth and guidance in the developing nervous system rely on intracellular membrane dynamics that involve endosome maturation and transport, as well as its regulated tethering to the endoplasmic reticulum (ER). Recent studies have identified several key molecules, such as protrudin, which plays a dynamic role at membrane contact sites between the ER and endosomes/lysosomes, and myosin Va, which acts as a sensor for ER-derived Ca that triggers peri-ER membrane export. These molecules form different types of multiprotein complexes at the interface of organelles and, in response to their surrounding microenvironments, such as Ca concentrations and lipid contents, regulate the directional movement of endosomal vesicles in extending axons.

Comparison of speech perception lists used to evaluate Japanese single syllable hearing.

Objective: In Japan, the 57S and 67S single syllable lists have been used to test speech perception in cochlear implant (CI) users. However, due to advances in implants and processors, these lists have become too simple for CI users. In 2019, the Japan Otological Society created a new list, referred to as the iCI2004.

Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals.

Cytomegalovirus (CMV) causes clinical issues primarily in immune-suppressed conditions. CMV-associated anterior uveitis (CMV-AU) is a notable new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals. As patient demographics indicated contributions from genetic background and immunosenescence as possible underlying pathological mechanisms, we analyzed the immunogenetics of the cohort in conjunction with cell phenotypes to identify molecular signatures of CMV-AU.

Lipid Transfer-Dependent Endosome Maturation Mediated by Protrudin and PDZD8 in Neurons.

Endosome maturation refers to the conversion of early endosomes (EEs) to late endosomes (LEs) for subsequent fusion with lysosomes. It is an incremental process that involves a combination of endosome fusion and fission and which occurs at contact sites between endosomes and the endoplasmic reticulum (ER), with knowledge of the underlying mechanisms having increased greatly in recent years. Protrudin is an ER-resident protein that was originally shown to regulate neurite formation by promoting endosome trafficking, whereas PDZD8 is a mammalian paralog of a subunit of the yeast ERMES (ER-mitochondrial encounter structure) complex that possesses lipid transfer activity.

Protrudin-deficient mice manifest depression-like behavior with abnormalities in activity, attention, and cued fear-conditioning.

Protrudin is a protein that resides in the membrane of the endoplasmic reticulum and is highly expressed in the nervous system. Although mutations in the human protrudin gene (ZFYVE27, also known as SPG33) give rise to hereditary spastic paraplegia (HSP), the physiological role of the encoded protein has been largely unclear. We therefore generated mice deficient in protrudin and subjected them to a battery of behavioral tests designed to examine their intermediate phenotypes.

Protrudin and PDZD8 contribute to neuronal integrity by promoting lipid extraction required for endosome maturation.

Endosome maturation depends on membrane contact sites (MCSs) formed between endoplasmic reticulum (ER) and endolysosomes (LyLEs). The mechanism underlying lipid supply for this process and its pathophysiological relevance remains unclear, however. Here, we identify PDZD8-the mammalian ortholog of a yeast ERMES subunit-as a protein that interacts with protrudin, which is located at ER-LyLE MCSs.

Predicting material properties by integrating high-throughput experiments, high-throughput ab-initio calculations, and machine learning.

High-throughput experiments (HTEs) have been powerful tools to obtain many materials data. However, HTEs often require expensive equipment. Although high-throughput ab-initio calculation (HTC) has the potential to make materials big data easier to collect, HTC does not represent the actual materials data obtained by HTEs in many cases.

Comprehensive hearing care network for early identification and intervention in children with congenital and late-onset/acquired hearing loss: 8 years' experience in Miyazaki.

Objective: In 2010, we established the Miyazaki Comprehensive Hearing Care Network (MCHCN) for early identification and intervention in children with congenital and late-onset/acquired hearing loss with the cooperation of related administrative bodies in Miyazaki prefecture. The central roles of the MCHCN program are played by the Hearing Care Center (HCC) at the University of Miyazaki Hospital established in 2010 to facilitate audiological diagnoses, hearing aid interventions, and educational efforts, as well as linkage with the Department of Otolaryngology for surgical interventions. Herein, we aimed to present the main outcomes of the MCHCN program organized by the HCC at the University of Miyazaki Hospital.

Roles of protrudin at interorganelle membrane contact sites.

Intracellular organelles were long viewed as isolated compartments floating in the cytosol. However, this view has been radically changed within the last decade by the discovery that most organelles communicate with the endoplasmic reticulum (ER) network via membrane contact sites (MCSs) that are essential for intracellular homeostasis. Protrudin is an ER resident protein that was originally shown to regulate neurite formation by promoting endosome trafficking.

Nuclear-cytoplasmic shuttling protein PP2A contributes to mTORC1-dependent dephosphorylation of FOXK1.

Mammalian target of rapamycin complex 1 (mTORC1) kinase is a master regulator of the cellular response to nutrition-related signals such as insulin and amino acids. mTORC1 is activated on the lysosomal membrane and induces phosphorylation of a variety of downstream molecules. We previously showed that activated mTORC1 induces protein phosphatase 2A (PP2A)-mediated dephosphorylation of the transcription factor forkhead box K1 (FOXK1).

The Autism-Related Protein CHD8 Cooperates with C/EBPβ to Regulate Adipogenesis.

The gene encoding the chromatin remodeler CHD8 is the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Heterozygous mutations in CHD8 give rise to ASD that is often accompanied by macrocephaly, gastrointestinal complaints, and slender habitus. Whereas most phenotypes of CHD8 haploinsufficiency likely result from delayed neurodevelopment, the mechanism underlying slender habitus has remained unknown.

TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1 activation.

Mammalian/mechanistic target of rapamycin complex 1 (mTORC1) responds to growth factors and nutrient availability. Amino acids induce the recruitment of mTORC1 to the lysosomal membrane and its consequent activation, but the molecular mechanism of such activation has remained unclear. We have now examined the role of TMEM55B, a lysosomal protein of unknown molecular function, in this process on the basis of the results of proteomics and immunofluorescence analyses showing that TMEM55B interacts with many proteins that participate in mTORC1 activation including components of the vacuolar-type proton ATPase (V-ATPase) and Ragulator complexes at the lysosomal membrane.

SRRM4-dependent neuron-specific alternative splicing of protrudin transcripts regulates neurite outgrowth.

Alternative splicing gives rise to diversity of the proteome, and it is especially prevalent in the mammalian nervous system. Indeed, many factors that control the splicing process govern nervous system development. Among such factors, SRRM4 is an important regulator of aspects of neural differentiation including neurite outgrowth.