Ask about this productRelated genes to: CLCC1 antibody
- Gene:
- CLCC1 NIH gene
- Name:
- chloride channel CLIC like 1
- Previous symbol:
- -
- Synonyms:
- MCLC
- Chromosome:
- 1p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2005-08-04
- Date modifiied:
- 2017-08-18
Related products to: CLCC1 antibody
Related articles to: CLCC1 antibody
- Orchestration of lipid production, storage and mobilization is vital for cellular and systemic homeostasis. Dysfunctional plasma lipid control represents the major risk factor for cardiometabolic diseases-the leading cause of human mortality. Within the cellular landscape, the endoplasmic reticulum (ER) is the central hub of lipid synthesis and secretion, particularly in metabolically active hepatocytes in the liver or enterocytes in the gut. Initially assembled in the ER lumen, lipid-ferrying lipoproteins necessitate the cross-membrane transfer of both neutral and phospholipids onto the lumenal apolipoprotein B (APOB), in a poorly defined process. Here we show that the ER protein CLCC1 regulates cellular lipid partition and, consequently, systemic lipid homeostasis by participating in trans-bilayer equilibration of phospholipids. CLCC1 partners with the phospholipid scramblase TMEM41B to recognize imbalanced bilayers and promote lipid scrambling, thereby supporting lipoprotein biogenesis and the subsequent bulk lipid transport. Loss of CLCC1 or TMEM41B leads to the emergence of giant lumenal lipid droplets enclosed by imbalanced ER bilayers and, consequently, accelerated pathogenesis of metabolic-dysfunction-associated liver steatohepatitis. The results reveal that phospholipid scrambling at the ER is essential for establishing a dynamic equilibrium. Considering the requirement of trans-bilayer phospholipid equilibration in numerous biological processes, ranging from catabolic autophagy to viral infection, we anticipate that future work will elucidate a homeostatic control mechanism intrinsic to ER function in lipid biogenesis and distribution. - Source: PubMed
Publication date: 2026/02/25
Wu LingzhiWang JianqinWang YaweiYang JunhanYao YuanhangWang YonglunHuang DongHu YatingXu XinxuanWang RenqianDu WenjingShi YitingLi QuanLiu LuZhu YuangangLi ShijieChen Feng-JungZhang XiuqinWang XiaoGuo QiangXu LiLi PengChen Xiao-Wei - Imbalances in lipid storage and secretion lead to hepatic steatosis, the accumulation of lipid droplets in hepatocytes. Our understanding of the mechanisms that govern the channelling of neutral lipids in hepatocytes towards cytosolic lipid droplets or secreted lipoproteins remains incomplete. Here we performed a series of CRISPR-Cas9 screens under different metabolic states that led to the identification of CLCC1 as a critical regulator of neutral lipid storage and secretion in hepatocytes. Loss of CLCC1 resulted in the buildup of large lipid droplets in hepatoma cells and Clcc1 knockout in mice caused liver steatosis. Lipid droplets were present in the lumen of the endoplasmic reticulum of the Clcc1-knockout hepatocytes and exhibited properties of lipoproteins, indicating a profound shift in neutral lipid flux. The loss of CLCC1 also led to the accumulation of nuclear membrane herniations accompanied by a reduction in nuclear pores. Remote homology searches identified a domain in CLCC1 that is homologous to yeast Brl1 and Brr6, factors that promote nuclear envelope fusion during nuclear pore complex assembly. Molecular dynamics simulations and mutagenesis studies support a model in which CLCC1 mediates membrane bending and fusion. We propose that CLCC1 mediates membrane fusion to promote hepatic neutral lipid flux and nuclear pore complex assembly. - Source: PubMed
Publication date: 2026/02/25
Mathiowetz Alyssa JMeymand Emily SParlakgül Güneşvan Hilten NiekTorres Emily FArtico Leonardo LDeol Kirandeep KLange MikePang Stephany PDoubravsky Cody ERoberts Melissa AJorgens Danielle MZalpuri ReenaKang MisunBoone CasadoraParks Brian WZhang YaohuanMorgens David WNewman Emily TsoZhou YingjiangTalukdar SaswataGrabe MichaelKu GregoryLevine Tim PArruda Ana PaulaOlzmann James A - Herpesvirales are an ancient viral order that causes lifelong infections in species from mollusks to humans. They export their capsids from the nucleus to the cytoplasm by a noncanonical nuclear egress route that involves capsid budding at the inner nuclear membrane followed by fusion of this temporary envelope with the outer nuclear membrane. Here, using a whole-genome CRISPR screen, we identify ER protein CLCC1 as important for the fusion stage of nuclear egress in herpes simplex virus 1. We also find that the genomes of Herpesvirales that infect mollusks and fish encode CLCC1 genes acquired from host genomes by horizontal gene transfer. In uninfected cells, loss of CLCC1 causes a nuclear blebbing defect, suggesting a role in host nuclear export. We hypothesize that CLCC1 facilitates an ancient cellular membrane fusion mechanism that Herpesvirales have hijacked or co-opted for capsid export and propose a mechanistic model. - Source: PubMed
Publication date: 2025/11/21
Dai BingSperl Adrian WPolack LucasMejia IsabelDame HaleyHuynh TienDeveney ChloeLavoie NathalieLee ChanyoungDoench John GDaugherty Matthew DHeldwein Ekaterina E - Cholestatic liver disease is characterized by highly accumulated bile acids and cholangiocyte proliferation, resulting in the development of fibrosis, cirrhosis, and ultimately liver failure necessitating liver transplantation. Calcium (Ca) signaling is commonly dysregulated in cholestasis and serves as an important regulator mediating cell proliferation. However, the role of Ca-mediated cholangiocyte proliferation and treatment strategies in bile duct ligation (BDL)-induced liver injury remains poorly understood. By integrating transcriptomic analysis with molecular biology techniques, we explored the mechanisms of liver injury across BDL animal models, primary cholangiocytes, and human intrahepatic biliary epithelial cholangiocytes. Here, we found that a natural ingredient, senkyunolide A (SenA), effectively alleviated cholestasis-induced Ca release from ER by inhibiting RYR channel, thereby preventing FIP200-mediated ER autophagy in response to Ca transients on the cytosolic ER surface. Increased cytosolic Ca further triggered ER stress, cholangiocyte cycle progression, and ductular reaction (DR). Importantly, SenA reversed the above process through its binding to chloride Channel CLIC Like 1 (CLCC1) for ubiquitination, thereby inhibiting CLCC1 activity and ER Ca release. si-CLCC1-loaded liposomes targeting cholangiocytes enhanced the anti-DR effects of SenA. Collectively, by controlling ER release of Ca in cholangiocytes, SenA presents potential for the development of therapeutic strategies aimed at addressing cholestatic fibrosis. SenA inhibited Ca-mediated cholangiocyte proliferation by binding to and promoting the ubiquitination of CLCC1, thereby alleviating cholestatic liver fibrosis. - Source: PubMed
Publication date: 2025/07/15
Li Ya-JingGuo Meng-YuQin Wen-QingLi Jia-NanLi Yu-FeiZhang Fu-KunXue Xiao-YongLi ShuoQu Jiao-RongLiu Run-PingWang LeiLi Xiao-Jiao-Yang - are an ancient viral order that infects species from mollusks to humans for life. During infection, these viruses translocate their large capsids from the nucleus to the cytoplasm independently from the canonical route through the nuclear pore. Instead, capsids dock at the inner nuclear membrane and bud into the perinuclear space. These perinuclear enveloped virions fuse with the outer nuclear membrane releasing the capsids into the cytoplasm for maturation into infectious virions. The budding stage is mediated by virally encoded proteins. But the mediator of the subsequent fusion stage is unknown. Here, using a whole-genome CRISPR screen with herpes simplex virus 1, we identified CLCC1 as an essential host factor for the fusion stage of nuclear egress. Loss of CLCC1 results in a defect in nuclear egress, accumulation of capsid-containing perinuclear vesicles, and a drop in viral titers. In uninfected cells, loss of CLCC1 causes a defect in nuclear pore complex insertion. Viral homologs of CLCC1 are present in herpesviruses that infect mollusks and fish. Our findings uncover an ancient cellular membrane fusion mechanism important for the fundamental cellular process of nuclear envelope morphogenesis that herpesviruses hijack for capsid transport. - Source: PubMed
Publication date: 2024/09/23
Dai BingPolack LucasSperl AdrianDame HaleyHuynh TienDeveney ChloeLee ChanyoungDoench John GHeldwein Ekaterina E