Abstract：
:Niemann-Pick disease type C (NPC) is an inherited lipid storage disorder caused by mutations in NPC1 or NPC2. NPC1 is a polytopic glycoprotein that contains a sterol-sensing domain, whereas NPC2 is a soluble protein that contains an MD-2-like lipid-recognition domain. In the current study, we addressed the hypothesis that ubiquitylation of NPC1 might be regulated by cholesterol. We found that depletion of cellular cholesterol facilitated ubiquitylation of NPC1 expressed in COS cells. A loss-of-function mutant, NPC1(P691S), which contains an amino acid substitution in the sterol-sensing domain, failed to respond to cholesterol depletion. Another mutant, NPC1(deltaLLNF), which lacks the endosomal-targeting motif, also failed to respond. SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1. SKD1(E235Q) associated with NPC1 on the endosomal membrane, whereas wild-type SKD1 associated with NPC1 only when cells were depleted of cholesterol. Similarly, in control human skin fibroblasts, cholesterol depletion facilitated ubiquitylation of endogenous NPC1. In patient cells that lack NPC2 function, NPC1 was ubiquitylated regardless of cellular cholesterol levels, suggesting that NPC2 is required to prevent NPC1 ubiquitylation under cholesterol-rich conditions. These results suggest that ubiquitylation of NPC1 and its association with the ESCRT complex are controlled by endosomal cholesterol levels utilizing a mechanism that involves NPC2.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Ohsaki Y,Sugimoto Y,Suzuki M,Hosokawa H,Yoshimori T,Davies JP,Ioannou YA,Vanier MT,Ohno K,Ninomiya Hdoi
10.1242/jcs.02993subject
Has Abstractpub_date
2006-07-01 00:00:00pages
2643-53issue
Pt 13eissn
0021-9533issn
1477-9137pii
jcs.02993journal_volume
119pub_type
杂志文章abstract：:Vertebrate nuclear lamins form a multigene family with developmentally controlled expression. In contrast, invertebrates have long been thought to contain only a single lamin, which in Drosophila is the well-characterized lamin Dm0. Recently, however, a Drosophila cDNA clone (pG-IF) has been identified that codes for ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:HEK293 cells expressing wild-type CXCR2 recruit PH-Akt-GFP to the leading edge of the cell in response to chemokine. However, in cells expressing mutant CXCR2 defective in AP-2 and HIP binding, i.e. with a mutation in the LLKIL motif, PH-Akt-GFP does not localize to the leading edge in response to ligand. Inhibition o...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01398
更新日期：2004-11-01 00:00:00
abstract：:It has long been established that neuronal growth cone navigation depends on changes in microtubule (MT) and F-actin architecture downstream of guidance cues. However, the mechanisms by which MTs and F-actin are dually coordinated remain a fundamentally unresolved question. Here, we report that the well-characterized ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.224311
更新日期：2019-04-30 00:00:00
abstract：:Annexin 1 is a Ca(2+)-regulated membrane binding protein and a major substrate of the epidermal growth factor receptor kinase. Because of its properties and intracellular distribution, the protein has been implicated in endocytic trafficking of the receptor, in particular in receptor sorting occurring in multivesicula...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-11-01 00:00:00
abstract：:A tissue culture system for epithelial cells derived from male human foetal genital ducts has been established. The cells show morphological and biochemical characteristics of ductal epithelial cells, and can be passaged and maintained in culture for considerable periods of time. These cells will provide a suitable sy...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:A heterogenous population of intact chondrons extracted from low-speed homogenates of canine tibial cartilage were stained by indirect immunofluorescence methods with a polyclonal antibody to type VI collagen. In each of the four chondron groups examined, anti-(type VI collagen) anti-serum was concentrated in the caps...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:C-CAM is a Ca(2+)-independent cell adhesion molecule (CAM) that mediates intercellular adhesion of isolated rat hepatocytes. It is widely distributed in epithelia, where its presence both at lateral cell borders and on apical cell surfaces suggests that it may have diverse biological functions. Two major isoforms, C-C...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:Elementary Ca(2+) signals, such as "Ca(2+) puffs", which arise from the activation of inositol 1,4,5-trisphosphate receptors, are building blocks for local and global Ca(2+) signalling. We characterized Ca(2+) puffs in six cell types that expressed differing ratios of the three inositol 1,4,5-trisphosphate receptor is...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-11-01 00:00:00
abstract：:Quantitative information about the range of influence of extracellular signaling molecules is critical for understanding their effects, but is difficult to determine in the complex and dynamic three-dimensional environment of a living embryo. Drosophila germ cells migrate during embryogenesis and use spatial informati...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.136176
更新日期：2013-12-01 00:00:00
abstract：:In neutrophils and other phagocytic cells, the small GTPase Rac is an essential regulator of a multi-component NADPH oxidase that produces high levels of superoxide, which kills invading pathogens. In many other cell types, Rac and newly discovered relatives of the neutrophil burst oxidase and its subunits have been f...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00937
更新日期：2004-01-15 00:00:00
abstract：:The alternative lengthening of telomeres (ALT) mechanism allows cancer cells to escape senescence and apoptosis in the absence of active telomerase. A characteristic feature of this pathway is the assembly of ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs) at telomeres. Here, we dissected the role of...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.148296
更新日期：2015-05-15 00:00:00
abstract：:We investigated the role of Pav-KLP, a kinesin-6, in the coordination of spindle and cortical dynamics during mitosis in Drosophila embryos. In vitro, Pav-KLP behaves as a dimer. In vivo, it localizes to mitotic spindles and furrows. Inhibition of Pav-KLP causes defects in both spindle dynamics and furrow ingression, ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.064048
更新日期：2010-06-01 00:00:00
abstract：:Occludin plays an important role in maintaining tight junction barrier function in many types of epithelia. We previously reported that activation of transient receptor potential vanilloid subtype 1 (TRPV1) in rabbit submandibular gland promoted salivary secretion, partly by an increase in paracellular permeability. W...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.111781
更新日期：2013-03-01 00:00:00
abstract：:The DNA content of isolated micronuclei, differentiating macronuclei (macronuclear Anlagen), and adult macronuclei of Loxodes magnus was measured cytofluorimetrically in preparations stained with a Schiff-type reagent, auramine-SO2, following hydrochloric acid hydrolysis. The DNA content of the youngest macronuclear A...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-08-01 00:00:00
abstract：:The molecular motor dynein is essential for mitotic spindle orientation, which defines the axis of cell division. The light intermediate chain subunits, LIC1 and LIC2, define biochemically and functionally distinct vertebrate dynein complexes, with LIC2-dynein playing a crucial role in ensuring spindle orientation. We...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.239673
更新日期：2020-06-23 00:00:00
abstract：:Barrier junctions prevent pathogen invasion and restrict paracellular leakage across epithelial sheets. To understand how one barrier junction, the septate junction (SJ), is regulated in vivo, we used fluorescence recovery after photobleaching (FRAP) to examine SJ protein dynamics in Drosophila. Most SJ-associated pro...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.087700
更新日期：2011-08-15 00:00:00
abstract：:Promyelocytic leukemia nuclear bodies (PML-NBs) are mobile subnuclear organelles formed by PML and Sp100 protein. They have been reported to have a role in transcription, DNA replication and repair, telomere lengthening, cell cycle control and tumor suppression. We have conducted high-resolution 4Pi fluorescence laser...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.053496
更新日期：2010-02-01 00:00:00
abstract：:Microscopic green algae inhabiting desert microbiotic crusts are remarkably diverse phylogenetically, and many desert lineages have independently evolved from aquatic ancestors. Here we worked with five desert and aquatic species within the family Scenedesmaceae to examine mechanisms that underlie desiccation toleranc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.212233
更新日期：2018-04-10 00:00:00
abstract：:When the human red cell consumes its ATP, the cell loses its discoid character in favour of a spiculated and eventually a spherical form. This discocyte-echinocyte transformation parallels both degradation of phosphatidylinositol 4,5-bisphosphate and phosphatidic acid but not dephosphorylation of cytoskeletal proteins...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1986-02-01 00:00:00
abstract：:The extracellular matrix (ECM) regulates cell behavior by influencing cell proliferation, survival, shape, migration and differentiation. Far from being a static structure, the ECM is constantly undergoing remodeling--i.e. assembly and degradation--particularly during the normal processes of development, differentiati...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.006064
更新日期：2008-02-01 00:00:00
abstract：:Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic human disease, with around 12.5 million people affected worldwide. ADPKD results from mutations in either PKD1 or PKD2, which encode the atypical G-protein coupled receptor polycystin-1 (PC1) and the transient receptor potential channel ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.211342
更新日期：2018-06-06 00:00:00
abstract：:Endothelial cells are known to undergo transitions in cell shape during long-term culture. Thus, the assumption that the separate phenotypes of microvascular endothelial cells (MVEC) recently isolated from bovine corpus luteum represent constitutively different cell strains cannot automatically be made. For this reaso...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:The protein product of the gene responsible for ocular albinism type 1, named OA1, is a pigment-cell-specific membrane glycoprotein, displaying features of G-protein-coupled receptors, yet exclusively localized to late endosomes, lysosomes and melanosomes. To dissect the signals responsible for the intracellular local...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02930
更新日期：2006-05-15 00:00:00
abstract：:Directed axonal growth depends on correct coordination of the actin and microtubule cytoskeleton in the growth cone. However, despite the relatively large number of proteins implicated in actin-microtubule crosstalk, the mechanisms whereby actin polymerization is coupled to microtubule stabilization and advancement in...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.203455
更新日期：2017-08-01 00:00:00
abstract：:Dynamins are a conserved family of proteins involved in membrane fusion and fission. Although mammalian dynamins are known to be involved in several membrane-trafficking events, the role of dynamin-1 in endocytosis is the best-characterised role of this protein family. Despite many similarities between endocytosis in ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.070508
更新日期：2010-10-15 00:00:00
abstract：:The redox status of human spermatozoa was found to have a profound influence on the fertilizing potential of these cells in association with qualitative and quantitative changes in the patterns of tyrosine phosphorylation. In general, oxidizing conditions enhanced tyrosine phosphorylation and stimulated sperm function...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-05-01 00:00:00
abstract：:Electron-microscope autoradiography has been used to obtain information on the localization of DNA labelled with [3H]thymidine in chloroplasts known to be replicating and concomitantly synthesizing and segregating DNA, in cultured leaf disks. The studies were made using both Microdol-X developer and a 'compact' develo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-03-01 00:00:00
abstract：:Ena/VASP proteins are actin-binding proteins that localize to actin stress fibres, the tips of filopodia and the lamellipodial leading edge. In the past few years, a number of seemingly conflicting studies have confused the Ena/VASP field, pointing to roles for these proteins in both promotion and inhibition of actin-...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00218
更新日期：2002-12-15 00:00:00
abstract：:Treatment of cells arrested in the cell cycle at the G1/S-phase boundary with 5 mM caffeine induces premature mitosis, resulting in chromosomal fragmentation and detachment of centromere-kinetochore fragments, which are subsequently attached to the mitotic spindle and segregated in anaphase. Taking advantage of this i...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:We investigated at the electron microscope level the fate of the three intranuclear structures known to accumulate snRNPs, and which correspond to the punctuate immunofluorescent staining pattern (the coiled bodies, the clusters of interchromatin granules and the interchromatin granule-associated zones) after exposure...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
