The heterogeneity of the endoplasmic reticulum (ER) makes it a versatile platform for a broad range of homeostatic processes, ranging from calcium regulation to synthesis and trafficking of proteins and lipids. It is not surprising that neurons use this organelle to fine-tune synaptic properties and thereby provide specificity to synaptic inputs. In this review, we discuss the mechanisms that enable activity-dependent ER recruitment into dendritic spines, with a focus on molecular mechanisms that mediate transport and retention of the ER in spines. The role of calcium signaling in spine ER, synaptopodin 'tagging' of active synapses, and the formation of the spine apparatus (SA) are highlighted. Finally, we discuss the role of liquid-liquid phase separation as a possible driving force in these processes.
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http://dx.doi.org/10.1016/j.tins.2022.10.012 | DOI Listing |
PLoS Genet
January 2025
Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st St. SW, Rochester, Minnesota 55905, United States of America.
Motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy, involve loss of muscle control resulting from death of motor neurons. Although the exact pathogenesis of these syndromes remains elusive, many are caused by genetically inherited mutations. Thus, it is valuable to identify additional genes that can impact motor neuron survival and function.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China.
Despite substantial advances in the antitumor effects of annonaceous acetogenins (ACGs), the absence of a defined biological action mechanism remains a major barrier to their clinical application. Here, it is found that squamocin effectively depletes both EZH2 and MYC in multiple cancer cell lines, including head and neck squamous cell carcinoma, and gastric and colorectal cancer, demonstrating potent efficacy in suppressing these in vivo tumor models. Through the combination of surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and cellular thermal shift assay (CETSA), heat shock protein 90α (HSP90α) is identified as the direct binding target of squamocin.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Viruses engage in a variety of processes to subvert host defenses and create an environment amenable to replication. Here, using rotavirus as a prototype, we show that calcium conductance out of the endoplasmic reticulum by the virus encoded ion channel, , induces intercellular calcium waves that extend beyond the infected cell and contribute to pathogenesis. Viruses that lack the ability to induce this signaling show diminished viral shedding and attenuated disease in a mouse model of rotavirus diarrhea.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.
Recombinant adeno-associated virus (rAAV) has emerged as one of the best gene delivery vectors for human gene therapy in vivo. However, the clinical efficacy of rAAV gene therapy is often hindered by the host immune response against its transgene products. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is specialised to process peptides presented by class I molecules of major histocompatibility complex.
View Article and Find Full Text PDFAm J Transl Res
December 2024
Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University Tianjin 300070, China.
Proteinase-activated receptor-2 (PAR2) is closely linked to tumor malignancy, but its biological role in cancer remains underexplored. In this study, we assessed PAR2 expression in lung adenocarcinoma (LUAD) and normal lung tissues, analyzed associations between clinicopathological features and survival rates, and confirmed that PAR2 promotes apoptosis resistance and reduces cisplatin-induced cytotoxicity in lung cancer cells. Using TCGA datasets, western blotting, qPCR, and immunohistochemistry (IHC), we observed a significant increase in PAR2 levels in LUAD samples compared to normal tissues (P<0.
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