Ask about this productRelated genes to: EXOC5 Blocking Peptide
- Gene:
- EXOC5 NIH gene
- Name:
- exocyst complex component 5
- Previous symbol:
- SEC10L1
- Synonyms:
- SEC10, SEC10P
- Chromosome:
- 14q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-09
- Date modifiied:
- 2015-08-25
Related products to: EXOC5 Blocking Peptide
Related articles to: EXOC5 Blocking Peptide
- Intracellular trafficking of amyloid precursor protein (APP) critically influences amyloidogenic processing, yet the mechanisms regulating this pathway remain incompletely defined. The exocyst is a highly conserved, insulin-responsive, eight-protein Rab effector complex that directs intracellular transport vesicle targeting and docking. We identified APP in a proteomics screen of neuronal cell surface proteins altered after chemical inhibition of exocyst activity. In SH-SY5Y cells expressing a mutant APP that enhances amyloidogenic processing, RNAi-mediated silencing of exocyst subunits significantly decreased sAPP and Aβ secretion, leading to significant intracellular APP accumulation. We found high-resolution co-localization of APP with exocyst subunits in soma and neurites of differentiated human SH-SY5Y neurons and mouse primary hippocampal neurons, and live-cell TIRF microscopy identified highly coordinated movement between fluorescently-tagged exocyst and APP proteins. These interactions were confirmed in these cells and in mouse brain histological sections by proximity ligation assays (PLAs) demonstrating close (<40nm) APP-EXOC5 association. To examine if exocyst activity in neurons is regulated by insulin, as it is in adipocytes and muscle, we generated a SH-SY5Y cell line with pHluorin-tagged GLUT4. Inhibition of the exocyst prevented exocytosis of GLUT4 to the plasma membrane in response to insulin. Additionally, using PLAs in mouse primary hippocampal neurons and SH-SY5Y neurons, we found that GLUT4-EXOC5 associations were increased by insulin signaling, but APP-EXOC5 associations were markedly reduced, indicating insulin-dependent retargeting of the exocyst complex away from APP+ vesicles towards GLUT+ vesicles. All together, these data identify the exocyst as a novel insulin-regulated mediator of neuronal APP trafficking and Aβ secretion. - Source: PubMed
Publication date: 2026/04/17
Balaan ChantellPatwardhan Geetika YSachs Rachel KKumasaka HannaSadagopan SwasthitaAou ShionLee Amanda JNelson Luke THew Brian EOwens Jesse BPolgar NoemiOrtega Michael ANichols Robert AFogelgren Ben - Impaired cell proliferation causes fibrotic changes in tissues, leading to loss of function. Although exocyst component 5 (Exoc5), a central component of the eight-protein exocyst complex, regulates the targeting and docking of intracellular vesicles which are essential for cell proliferation, its role in tissue regeneration remains to be defined. Here, we investigated the role of Exoc5 in the repair of kidney injury induced by ischemia-reperfusion (I/R) using proximal tubule cell (PTC)-specific Exoc5 knockout (Exoc5) mice generated by crossing Exoc5 with PEPCK-cre mice. Exoc5 and wild-type (Exoc5) mice were subjected to either bilateral kidney I/R or sham surgery. I/R induced functional and structural kidney damage in both Exoc5 and Exoc5 mice, as evidenced by increased plasma creatinine and BUN, decreased glomerular filtration rate, and histological damage. Kidney function and structure gradually improved in both Exoc5 and Exoc5 mice over time; however, neither group fully recovered normal function, and the recovery was less pronounced in Exoc5 than in Exoc5 mice. Twenty-one days after I/R, Exoc5 mice showed greater collagen deposition and α-smooth muscle actin (α-SMA) and vimentin expression compared to Exoc5 mice, whereas E-cadherin expression was lower. Post-I/R PTC proliferation in Exoc5 mice was significantly lower than in Exoc5 mice. In contrast, post-I/R induction of paired box 2 (Pax2) was greater in Exoc5 than in Exoc5 mice. In HK-2 cells, a human PTC line, Exoc5 downregulation by siRNA increased Pax2 expression and further increased N-cadherin, phosphorylated-Smad3 (p-Smad3), and α-SMA expression compared to control cells following TGF-β treatment. Collectively, these findings indicate that loss of Exoc5 impairs PTC regeneration and exacerbates fibrosis in the injured kidney, suggesting its therapeutic potential in preventing the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). - Source: PubMed
Publication date: 2026/04/24
Lim Hui JaeKong Min JungNoh MiraPark You RiHan Yong KwonLipschutz Joshua HPark Kwon Moo - EXOC5/SEC10, the central subunit of the exocyst complex, is crucial for the trafficking of secretory vesicles to the plasma membrane. However, its role in innate immunity and viral replication remains unclear. Here we demonstrate that EXOC5 acts as a negative regulator of DNA virus-triggered CGAS-STING1 signaling via targeting STING1. Mechanistically, EXOC5 facilitates the autophagic degradation of STING1 via K63-linked polyubiquitination at Lys224 and Lys338 by the E3 ligase TRIM56, which serves as a recognition signal for the cargo receptor SQSTM1/p62 (sequestosome 1). Furthermore, EXOC5 inhibits antiviral innate immunity and promotes viral replication via EXOC5-TRIM56-STING1-SQSTM1 signal transduction. More importantly, myeloid-specific deletion of in mice improves survival and reduces viral load. In general, these findings revealed a negative feedback loop of type I interferon signaling through the EXOC5-TRIM56-STING1-SQSTM1 axis, which has the potential to serve as a new target for the development of antiviral therapeutics that regulate the host immune response. BafA1: bafilomycin A1; BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; EXOC5/SEC10: exocyst complex component 5; HAdV-4: human adenovirus type 4; HSV-1: herpes simplex virus type 1; HT-DNA: herring testis deoxyribonucleic acid; IFN: interferon; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; PMs: peritoneal macrophages; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; VACV70: 70-mers of dsDNA representing the genome of vaccinia virus. - Source: PubMed
Publication date: 2026/04/17
Ma WenqingXu YananYu JieSun FachaoYu XiaoHe LutengLi YingyingHe Daniel ChangWang HongmeiHe Hongbin - SEC10 (EXOC5), a central subunit of the exocyst complex, plays a critical role in vesicle trafficking. However, its function in bovine herpesvirus 1 (BoHV-1) triggered-antiviral innate immunity and viral replication remains unclear. In this study, we identify SEC10 as a key negative regulator of antiviral immune responses. SEC10 suppresses the transcriptional expression of JAK1, thereby significantly impairing activation of the JAK-STAT signaling pathway, dampening type I interferon (IFN-I)-mediated antiviral immunity, and promoting BoHV-1 replication. Mechanistically, SEC10 downregulates the expression of the transcription factor KLF15 and subsequently modulates JAK1 transcription in a KLF15-dependent manner, establishing a "SEC10-KLF15-JAK1" regulatory axis. Collectively, our findings not only reveal SEC10 as a novel immunomodulatory factor but also uncover a previously unrecognized KLF15-dependent transcriptional mechanism that fine-tunes innate immune responses. This work provides new insights into the complex regulatory network of the JAK-STAT signaling pathway and identifies a potential therapeutic target for combating BoHV-1 infection. - Source: PubMed
Publication date: 2026/03/26
Ma WenqingYu XiaoXu YananSun FachaoZhao MengruiWang XinleiHuan YanjunYin XinWang HongmeiHe Hongbin - Fibrosis, an undesirable side effect of the repair process, is due to aberrant cell differentiation and is a typical cause of progressive diseases including chronic kidney disease (CKD). Exocyst complex component 5 (Exoc5), a central component of the highly-conserved eight-protein exocyst complex, is involved in cell differentiation and maturation; however, the role of Exoc5 in fibrosis remains to be defined. Here we investigate the role and underlying molecular mechanisms of Exoc5 on kidney development and fibrosis using kidney proximal tubule cell-specific Exoc5-knockout (PT-Exoc5) mice generated by crossing Exoc5 with PEPCK-cre mice. Exoc5-knockout mice showed normal kidney structure and function. Unilateral ureteral obstruction (UUO) led to kidney fibrosis with decreased Exoc5 expression, and Exoc5 knockout worsened the fibrosis. Exoc5 knockout alone increased Yes-associated protein (YAP) expression and exacerbated UUO-induced YAP activation and the expression of CTGF and CYR61, products of YAP, compared with wild-type (PT-Exoc5) mice. UUO induced paired box 2 (Pax2, which is mainly expressed during kidney development) expression in both mice, and the UUO-induced Pax2 expression in PT-Exoc5 was greater than in PT-Exoc5 mice. In HK-2 cells, a human proximal tubule cell, EXOC5 downregulation by siRNA increased YAP and Pax2 expression. EXOC5 downregulation augmented TGF-β-induced YAP activation and epithelial-to-mesenchymal transition. Taken together, our data demonstrate that Exoc5 plays a protective role in kidney fibrosis, implying that Exoc5 could potentially serve as a therapeutic target for the regulation of fibrosis. - Source: PubMed
Publication date: 2026/03/04
Lim Hui JaeHan Yong KwonNoh Mi RaPark You RiJang Se YoungLipschutz Joshua HPark Kwon Moo