Lamp1

There is accumulating evidence that pathogenic T cells in T1D recognize epitopes formed by post-translational modifications of β-cell antigens, including hybrid insulin peptides (HIPs). The ligands for several CD4 T-cell clones derived from the NOD mouse are HIPs composed of a fragment of proinsulin joined to peptides from endogenous β-cell granule proteins. The diabetogenic T-cell clone BDC-6.9 reacts to a fragment of C-peptide fused to a cleavage product of pro-islet amyloid polypeptide (6.9HIP)...

Acinetobacter baumannii (A. baumannii) causes autophagy flux disorder by degrading STX17, resulting in a serious inflammatory response. It remains unclear whether STX17 can alter the inflammatory response process by controlling autolysosome function. This study aimed to explore the role of STX17 in the regulation of pyroptosis induced by A. baumannii. Our findings indicate that overexpression of STX17 enhances autophagosome degradation, increases LAMP1 expression, reduces Cathepsin B release, and improves lysosomal function...

PURPOSE/STUDY QUESTION: Does piercing oocyte membranes during ICSI allow the influx of surrounding zwitterionic buffer into human oocytes and result in altered developmental competence? METHODS: Human oocytes directed to IRB-approved research were used to determine the unrestricted influx of surrounding buffer into the oocyte after piercing of membranes via confocal fluorescence microscopy (n = 80 human MII oocytes) and the influence of the select buffer influx of HEPES, MOPS, and bicarbonate buffer on the oocyte transcriptome using ultra-low input RNA sequencing (n = 40 human MII oocytes)...

BRAFV600E is the most prevalent mutation in thyroid cancer and correlates with poor prognosis and therapy resistance. Although selective inhibitors of BRAFV600E have been developed, more advanced tumors such as anaplastic thyroid carcinomas show a poor response in clinical trials. Therefore, the study of alternative survival mechanisms is needed. Since metabolic changes have been related to malignant progression, in this work we explore metabolic dependencies of thyroid tumor cells to exploit them therapeutically...

In overactive human osteoclasts, we previously identified an alternative splicing event in LGALS8 , encoding galectin-8, resulting in decreased expression of the long isoform. Galectin-8, which modulates cell-matrix interactions and functions intracellularly as a danger recognition receptor, has never been associated with osteoclast biology. In human osteoclasts, inhibition of galectin-8 expression revealed its roles in bone resorption, osteoclast nuclearity, and mTORC1 signaling regulation. Galectin-8 isoform-specific inhibition asserted a predominant role for the short isoform in bone resorption...

OBJECTIVE: To explore the involvement of TFEB-mediated autophagy-lysosomal mechanisms in multiple myeloma (MM) during bortezomib treatment. METHODS: MM cells were exposed to bortezomib or subjected to TFEB knockdown. CCK assay was used to assess the cell proliferation. Western blotting and fluorescent staining were conducted to examine autophagy and lysosomes. The TFEB expression pattern was analyzed, and whole transcriptome sequencing was carried out. Additionally, TFEB target genes were predicted using the GTRD(https://gtrd...

Bisphenol A (BPA) is a well-known environmental contaminant that can negatively impact reproductive function. Disruption of autophagy is implicated in BPA-induced cell injury, the specific molecular mechanisms through which BPA affects autophagy in Sertoli cells are still unknown. In the present study, TM4 cells were exposed to various doses of BPA (10, 100, and 200 μM), and the results indicated that BPA exposure led to the accumulation of autophagosomes, this change was accompanied by increased expression of p-mTOR and decreased expression of Atg12, a protein involved in regulating autophagy initiation...

Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) and trigger different types of cell death, including apoptosis. Newcastle disease virus (NDV) can naturally infect most birds. Additionally, it serves as a promising oncolytic virus known for its effective infection of tumor cells and induction of intensive apoptotic responses. However, the involvement of lysosomes in NDV-induced apoptosis remains poorly understood...

Neuronal ceroid lipofuscinosis (NCL), type 6 (CLN6) is a neurodegenerative disorder associated with progressive neurodegeneration leading to dementia, seizures, and retinopathy. CLN6 encodes a resident-ER protein involved in trafficking lysosomal proteins to the Golgi. CLN6p deficiency results in lysosomal dysfunction and deposition of storage material comprised of Nile Red + lipids/proteolipids that include subunit C of the mitochondrial ATP synthase (SUBC). White matter involvement has been recently noted in several CLN6 animal models and several CLN6 subjects had neuroimaging was consistent with leukodystrophy...

In the Drosophila larval salivary gland, developmentally programmed fusions between lysosomes and secretory granules (SGs) and their subsequent acidification promote the maturation of SGs that are secreted shortly before puparium formation. Subsequently, ongoing fusions between non-secreted SGs and lysosomes give rise to degradative crinosomes, where the superfluous secretory material is degraded. Lysosomal fusions control both the quality and quantity of SGs, however, its molecular mechanism is incompletely characterized...

Patients with sialidosis (mucolipidosis type I) type I typically present with myoclonus, seizures, ataxia, cherry-red spots, and blindness because of mutations in the neuraminidase 1 (NEU1) gene. Currently, there is no treatment for sialidosis. In this study, we developed an adeno-associated virus (AAV)-mediated gene therapy for a Neu1 knockout (Neu1-/- ) mouse model of sialidosis. The vector, AAV9-P3-NP, included the human NEU1 promoter, NEU1 cDNA, IRES, and CTSA cDNA. Untreated Neu1-/- mice showed astrogliosis and microglial LAMP1 accumulation in the nervous system, including brain, spinal cord, and dorsal root ganglion, together with impaired motor function...

Cervical cancer is a malignant tumor that occurs in the cervix of women and endangers their lives. In this study, we aimed to assess the roles of NUPR1 and TFE3 in cervical cancer. The Cancer Genome Atlas (TCGA) database was used to assess the correlation between NUPR1 and TFE3 expression in cervical cancer. By silencing NUPR1 and TFE3, and through 3-MA treatment, we determined whether their silencing could lead to lysosomal dysfunction, thereby inhibiting autophagy and cervical cancer cell proliferation. Their roles were further analyzed using molecular biological methods...

INTRODUCTION: Dehydrocostus lactone (Dehy), a natural sesquiterpene lactone from Saussurea lappa Clarke, displays remarkable efficacy in treating cancer and gastrointestinal disorders. However, its anti-gastric cancer (GC) effect remains poorly understood. OBJECTIVES: Our study aimed to elucidate the anti-GC effect of Dehy and its putative mechanism. METHODS: The anti-GC effect was assessed with MTT, colony formation, wound healing and transwell invasion assays...

Synapse loss is one of the most critical features in Alzheimer's disease (AD) and correlates with cognitive decline. Astrocytes mediate synapse elimination through multiple EGF-like domains 10 (MEGF10) pathways in the developing and adult brain to build the precise neural connectivity. However, whether and how astrocytes mediate synapse loss in AD remains unknown. We here find that the phagocytic receptor MEGF10 of astrocytes is significantly increased in vivo and in vitro, which results in excessive engulfment of synapses by astrocytes in APP/PS1 mice...

After spinal cord injury (SCI), the accumulation of myelin debris at the lesion exacerbates cell death and hinders axonal regeneration. Transplanted bone marrow mesenchymal stem cells (BMSCs) have been proven to be beneficial for SCI repair, but they are susceptible to apoptosis. It remains unclear whether this apoptotic process is influenced by myelin debris. Here, we constructed rat BMSCs overexpressing human B-cell lymphoma 2 (hBcl2) alone (hBcl2 group), BMSCs overexpressing hBcl2 with an endoplasmic reticulum-anchored segment (hBcl2-cb) (cb group), and a negative control group (NC group) for transplantation in this study...

To reach the lysosome, lysosomal membrane proteins (LMPs) are translocated in the endoplasmic reticulum after synthesis and then transported to the Golgi apparatus. The existence of a direct transport from the Golgi apparatus to the endosomes but also of an indirect route through the plasma membrane has been described. Clathrin adaptor binding motifs contained in the cytosolic tail of LMPs have been described as key players in their intracellular trafficking. Here we used the RUSH assay to synchronise the biosynthetic transport of multiple LMPs...

Entosis is a process that leads to the formation of cell-in-cell structures commonly found in cancers. Here, we identified entosis in hepatocellular carcinoma and the loss of Rnd3 (also known as RhoE) as an efficient inducer of this mechanism. We characterized the different stages and the molecular regulators of entosis induced after Rnd3 silencing. We demonstrated that this process depends on the RhoA/ROCK pathway, but not on E-cadherin. The proteomic profiling of entotic cells allowed us to identify LAMP1 as a protein upregulated by Rnd3 silencing and implicated not only in the degradation final stage of entosis, but also in the full mechanism...

Glycosylation changes in cancer proteins have been associated with malignant transformation. However, techniques for analyzing site-specific glycosylation changes in target proteins obtained from clinical tissue samples are insufficient. To overcome these problems, we developed a targeted N-glycoproteomic approach consisting of immunoprecipitation, glycopeptide enrichment, LC/MS/MS, and structural assignment using commercially available analytical software followed by manual confirmation. This approach was applied to the comparative site-specific glycosylation analysis of lysosome-associated membrane glycoprotein 1 (LAMP1) between breast cancer (BC) tumors and normal tissues adjacent to tumors...

The multisubunit HOPS tethering complex is a well-established regulator of lysosome fusion with late endosomes and autophagosomes. However, the role of the HOPS complex in other stages of endo-lysosomal trafficking is not well understood. To address this, we made HeLa cells knocked out for the HOPS-specific subunits Vps39 or Vps41, or the HOPS-CORVET-core subunits Vps18 or Vps11. In all four knockout cells we found that endocytosed cargos were trapped in enlarged endosomes that clustered in the perinuclear area...

Humans are usually exposed to nicotine through the use of tobacco products. Although it is generally believed that nicotine is relatively harmless in tobacco consumption, it is, in fact, a toxic substance that warrants careful consideration of its potential toxicity. However, the current understanding of the neurotoxicity of nicotine is still very limited. In this study, we aim to reveal the toxic risk of nicotine to key target neuronal cells and its potential toxic mechanisms. The results showed that nicotine induced cell death, ROS increase, mitochondrial membrane potential decrease, and DNA damage in SH-SY5Y human neuroblastoma cells at millimolar concentrations, but did not cause toxic effects at the physiological concentration...