Ask about this productRelated genes to: GORASP1 Blocking Peptide
- Gene:
- GORASP1 NIH gene
- Name:
- golgi reassembly stacking protein 1
- Previous symbol:
- GOLPH5
- Synonyms:
- GRASP65, P65, FLJ23443
- Chromosome:
- 3p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-11-02
- Date modifiied:
- 2016-10-05
Related products to: GORASP1 Blocking Peptide
Related articles to: GORASP1 Blocking Peptide
- The Golgi complex is central to cellular homeostasis and serves as a key processing and sorting hub for protein trafficking. In many cell types, the Golgi complex is organized as interconnected stacks of cisternae, forming a structure known as the Golgi ribbon. This ribbon undergoes dynamic remodelling during physiological processes, such as cell division, and under pathological conditions, including cancer and neurodegeneration. A critical step in the unlinking of the Golgi ribbon involves the phosphorylation of the stacking protein GRASP65, which leads to the separation of the ribbon into individual stacks, a process necessary for the G2/M transition of the cell cycle. However, existing tools for selectively manipulating the GRASP65 role in ribbon organization are limited by non-specific effects or technical challenges. Here, we present the development and characterization of a membrane-permeable peptide, R-GRASP65-S277, derived from GRASP65 and containing the phosphorylation site Ser277, which is essential for Golgi unlinking. This peptide effectively inhibited Golgi unlinking and mitotic entry in several cell lines, including cancer models. In contrast, a control peptide with a non-phosphorylatable alanine substitution (R-GRASP65-S277A) showed no such effect, confirming the specificity of the tool. Furthermore, the R-GRASP65-S277 peptide reversed Golgi unlinking induced by the chemotherapeutic agent doxorubicin, demonstrating its utility in studying stress-induced Golgi disassembly. These findings establish the R8-GRASP65-S277 peptide as a specific, potent, and scalable tool for probing the molecular mechanisms of Golgi unlinking, its regulation of cell cycle progression, and its potential contributions to pathological states. - Source: PubMed
Publication date: 2025/12/01
Cervigni Romina InesBonavita RaffaellaBarretta Maria LuisaSpano DanielaAyala InmaculadaMascanzoni FabiolaIannitti RobertaHenklein PetraMonti AlessandraRenna MaurizioDoti NunziannaColanzi Antonino - Taurine is an amino acid with several physiological functions and has been shown to be involved in the anti-tumor of human nasopharyngeal carcinoma (NPC) cells. However, the role of taurine metabolism-related genes (TMRGs) in NPC has not been reported. We integrated data from the Genecards, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Expression Omnibus(GEO) databases to identify differentially expressed genes associated with taurine metabolism in NPC patients. Gene Ontology (GO) and KEGG analyses were conducted to investigate the underlying mechanisms. Subsequently, Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct a taurine metabolism-related prognostic signature. Survival, medication sensitivity, and immunological microenvironment evaluations were performed to assess the prognostic utility of the model. Finally, immunohistochemistry (IHC) experiments were performed to validate the model's prognostic reliability. In addition, we further verified the reliability of our research results through molecular docking and single-cell sequencing. Our prognostic model was based on three pivotal TMRGs (ABCB1, GORASP1, and EZH2). Functional analysis revealed a strong association between TMRGs and miRNAs in cancer. Notably, increased risk scores correlated with worsening tumor malignancy and prognosis. Significant disparities in immune microenvironment, immune checkpoints, and drug sensitivity were observed between the high- and low-risk groups. The protein expression patterns of the selected genes in clinical NPC samples were validated using immunohistochemistry. Molecular docking verified the interaction between these three core genes and taurine, which was further supported by single-cell sequencing showing significant expression variation among different cell clusters in NPC. We had elucidated the functions, therapeutic potential, and prognostic significance of three key genes related to taurine metabolism in NPC through multidimensional research and experimental validation. This research provided valuable insights and potential avenues for improved NPC management. - Source: PubMed
Publication date: 2025/04/24
Feng ZhangYang YuhangLuo WenqiLi JinqingXie ZhenlianZuo LongDuan MeijiaoZuo DongzhiMo RuweiTang XuejingYi ShijiangHe XiaosongLiu FangxianMa NingHe Feng - GRASP65 is a Golgi-associated peripheral protein encoded by the gene and required for Golgi cisternal stacking in vitro. A key role of GRASP65 in the regulation of cell division has also been suggested. However, depletion of GRASP65 in mice has little effect on the Golgi structure and the gene has not been associated with any human phenotype to date. Here, we report the identification of the first human pathogenic variant of (c.1170_1171del; p.Asp390Glufs*18) in a patient combining a neurodevelopmental disorder with neurosensory, neuromuscular, and skeletal abnormalities. Functional analysis revealed that the variant leads to a total absence of GRASP65. The structure of the Golgi apparatus did not show fragmentation, but glycosylation anomalies such as hyposialylation were detected. Mitosis analyses revealed an excess of prometaphases and metaphases with polar chromosomes, suggesting a delay in the cell cycle. These phenotypes were recapitulated in RPE cells in which a similar mutation was introduced by CRISPR/Cas9. These results indicate that loss of GRASP65 in humans causes a novel Golgipathy associated with defects in glycosylation and mitotic progression. - Source: PubMed
Publication date: 2025/02/11
Lebon SophieBruneel ArnaudDrunat SéverineAlbert AlexandraCsaba ZsoltElmaleh MoniqueNtorkou AlexandraTénier YannFenaille FrançoisGressens PierrePassemard SandrineBoespflug-Tanguy OdileDorboz ImenEl Ghouzzi Vincent - The Golgi apparatus plays a crucial role in the delivery of lysosomal enzymes. Golgi reassembly stacking proteins, GRASP55 and GRASP65, are vital for maintaining Golgi structure and function. GRASP55 depletion results in the missorting and secretion of the lysosomal enzyme cathepsin D, though the mechanisms remain unclear. In this study, we conducted secretomic analyses of GRASP55 knockout cells and found a significant increase in lysosome-associated proteins in the extracellular medium. Using the lysosomal beta-hexosaminidase subunit alpha (HEXA) as a model, we found that GRASP55 depletion disrupted normal trafficking and processing of HEXA, resulting in increased secretion of the immature (pro-form) HEXA into the extracellular milieu, along with decreased levels of the mature form and enzymatic activity within the cell. GRASP55 depletion significantly reduced the complex formation between HEXA and mannose 6-phosphate (M6P) receptors (MPR), despite no overall change in MPR expression. Finally, we found there was a notable reduction in the expression of GNPTAB, leading to a reduction in M6P modification of HEXA, hindering its efficient targeting to lysosomes. These findings reveal the role of GRASP55 in regulating lysosomal enzyme dynamics, emphasizing its role in the sorting and trafficking of lysosomal proteins. - Source: PubMed
Publication date: 2025/01/22
Akaaboune Sarah ReemJaved AadilBui SarahWierenga AlissaWang Yanzhuang - Gap junctions formed by the major neuronal connexin Cx36 function as electrical synapses in the nervous system and provide unique functions such as synchronizing neuron activities or supporting network oscillations. Although the physiological significance of electrical synapses for neuronal networks is well established, little is known about the pathways that regulate the transport of its main component: Cx36. Here we have used HEK293T cells as an expression system in combination with siRNA and BioID screens to study the transition of Cx36 from the ER to the cis Golgi. Our data indicate that the C-terminal tip of Cx36 is a key factor in this process, mediating binding interactions with two distinct components in the early secretory pathway: the COPII complex and the Golgi stacking protein Grasp55. The C-terminal amino acid valine serves as an ER export signal to recruit COPII cargo receptors Sec24A/B/C at ER exit sites, whereas the PDZ binding motif "SAYV" mediates an interaction with Grasp55. These two interactions have opposing effects in their respective compartments. While Sec24 subunits carry Cx36 out of the ER, Grasp55 stabilizes Cx36 in the Golgi as shown in over expression experiments. These early regulatory steps of Cx36 are expected to be essential for the formation, function, regulation and plasticity of electrical synapses in the developing and mature nervous system. - Source: PubMed
Publication date: 2024/10/12
Tetenborg StephanAriakia FatemehMartinez-Soler ElizabethShihabeddin EyadLazart Ignacio CebrianMiller Adam CO'Brien John