Abstract:
:The mannose 6-phosphate (Man-6-P) lysosomal targeting signal on acid hydrolases is synthesized by the sequential action of uridine 5'-diphosphate-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase) and GlcNAc-1-phosphodiester alpha-N-acetylglucosaminidase ("uncovering enzyme" or UCE). Mutations in the two genes that encode GlcNAc-1-phosphotransferase give rise to lysosomal storage diseases (mucolipidosis type II and III), whereas no pathological conditions have been associated with the loss of UCE activity. To analyze the consequences of UCE deficiency, the UCE gene was inactivated via insertional mutagenesis in mice. The UCE -/- mice were viable, grew normally and lacked detectable histologic abnormalities. However, the plasma levels of six acid hydrolases were elevated 1.6- to 5.4-fold over wild-type levels. These values underestimate the degree of hydrolase hypersecretion as these enzymes were rapidly cleared from the plasma by the mannose receptor. The secreted hydrolases contained GlcNAc-P-Man diesters, exhibited a decreased affinity for the cation-independent mannose 6-phosphate receptor and failed to bind to the cation-dependent mannose 6-phosphate receptor. These data demonstrate that UCE accounts for all the uncovering activity in the Golgi. We propose that in the absence of UCE, the weak binding of the acid hydrolases to the cation-independent mannose 6-phosphate receptor allows sufficient sorting to lysosomes to prevent the tissue abnormalities seen with GlcNAc-1-phosphotranferase deficiency.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Boonen M,Vogel P,Platt KA,Dahms N,Kornfeld Sdoi
10.1091/mbc.e09-05-0398subject
Has Abstractpub_date
2009-10-01 00:00:00pages
4381-9issue
20eissn
1059-1524issn
1939-4586pii
E09-05-0398journal_volume
20pub_type
杂志文章abstract::In this essay I describe my personal journey from reductionist to systems cell biology and describe how this in turn led to a 3-year sea voyage to explore complex ocean communities. In describing this journey, I hope to convey some important principles that I gleaned along the way. I realized that cellular functions e...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-06-0571
更新日期:2012-07-01 00:00:00
abstract::In Saccharomyces cerevisiae, the class C vacuole protein sorting (Vps) proteins, together with Vam2p/Vps41p and Vam6p/Vps39p, form a complex that interacts with soluble N-ethylmaleimide-sensitive factor attachment protein receptor and Rab proteins to "tether" vacuolar membranes before fusion. To determine a role for t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-06-0358
更新日期:2004-03-01 00:00:00
abstract::Activation of the high-osmolarity glycerol (HOG) pathway for osmoregulation in the yeast Saccharomyces cerevisiae involves interaction of the adaptor Ste50p with the cytoplasmic tail of single-transmembrane protein Opy2p. We have determined the solution structure of the Ste50p-RA (Ras association) domain, and it shows...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-07-0645
更新日期:2009-12-01 00:00:00
abstract::When demembranated sperm nuclei are placed in a Xenopus egg extract, they become surrounded by a nuclear envelope and then swell to form morphologically typical pronuclei. Granules ranging from < 1.0 to approximately 3.0 microns in diameter appear within such nuclei. Bell et al. identified four nucleolar proteins in t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.5.6.633
更新日期:1994-06-01 00:00:00
abstract::Endocytosis modulates EGFR function by compartmentalizing and attenuating or enhancing its ligand-induced signaling. Here we show that it can also control the cell surface versus intracellular distribution of empty/inactive EGFR. Our previous observation that PKA inhibitors induce EGFR internalization prompted us to t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-02-0167
更新日期:2010-08-15 00:00:00
abstract::The mitochondrial cytochrome c oxidase assembles in the inner membrane from subunits of dual genetic origin. The assembly process of the enzyme is initiated by membrane insertion of the mitochondria-encoded Cox1 subunit. During complex maturation, transient assembly intermediates, consisting of structural subunits and...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-12-0811
更新日期:2016-05-15 00:00:00
abstract::Clathrin-mediated endocytosis is a fundamental cellular process conserved from yeast to mammals and is an important endocytic route for the internalization of many specific cargos, including activated growth factor receptors. Here we examined changes in tyrosine phosphorylation, a representative output of growth facto...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-07-0637
更新日期:2011-02-15 00:00:00
abstract::Polarized assembly of actin filaments forms the basis of actin-based motility and is regulated both spatially and temporally. Cells use a variety of mechanisms by which intrinsically slower processes are accelerated, and faster ones decelerated, to match rates observed in vivo. Here we discuss how kinetic studies of i...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-06-0352
更新日期:2016-01-01 00:00:00
abstract::Extended coiled-coil proteins of the Golgin family play prominent roles in maintaining the structure and function of the Golgi complex. Here we further investigate the Golgin protein Coy1 and document its function in retrograde transport between early Golgi compartments. Cells that lack Coy1 displayed a reduced half-l...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E17-03-0137
更新日期:2017-08-09 00:00:00
abstract::Centrioles and basal bodies are cylinders composed of nine triplet microtubule blades that play essential roles in the centrosome and in flagellar assembly. Chlamydomonas cells with the bld2-1 mutation fail to assemble doublet and triplet microtubules and have defects in cleavage furrow placement and meiosis. Using po...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e02-04-0205
更新日期:2002-11-01 00:00:00
abstract::Mitochondrial dysfunction is associated with the development of many age-related human diseases. Therefore recognizing and correcting the early signs of malfunctioning mitochondria is of critical importance for cellular welfare and survival. We previously demonstrated that VCP/Cdc48-associated mitochondrial stress res...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E13-02-0072
更新日期:2013-05-01 00:00:00
abstract::Hsk1, Saccharomyces cerevisiae Cdc7-related kinase in Shizosaccharomyces pombe, is required for G1/S transition and its kinase activity is controlled by the regulatory subunit Dfp1/Him1. Analyses of a newly isolated temperature-sensitive mutant, hsk1-89, reveal that Hsk1 plays crucial roles in DNA replication checkpoi...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.12.5.1257
更新日期:2001-05-01 00:00:00
abstract::In autosomal dominant polycystic kidney disease (ADPKD), cysts accumulate and progressively impair renal function. Mutations in PKD1 and PKD2 genes are causally linked to ADPKD, but how these mutations drive cell behaviors that underlie ADPKD pathogenesis is unknown. Human ADPKD cysts frequently express cadherin-8 (ca...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-01-0059
更新日期:2016-11-07 00:00:00
abstract::The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio a...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-07-0614
更新日期:2010-07-01 00:00:00
abstract::Targeted endocytosis of plasma membrane (PM) proteins allows cells to adjust their complement of membrane proteins to changing extracellular conditions. For a wide variety of PM proteins, initiation of endocytosis is triggered by ubiquitination. In yeast, arrestin-related trafficking adaptors (ARTs) enable a single ub...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-08-0570
更新日期:2016-12-15 00:00:00
abstract::Cohesion establishment and maintenance are carried out by proteins that modify the activity of Cohesin, an essential complex that holds sister chromatids together. Constituents of the replication fork, such as the DNA polymerase alpha-binding protein Ctf4, contribute to cohesion in ways that are poorly understood. To ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-09-0637
更新日期:2004-04-01 00:00:00
abstract::Three mitochondrial DNA-encoded proteins, Cox1, Cox2, and Cox3, comprise the core of the cytochrome c oxidase complex. Gene-specific translational activators ensure that these respiratory chain subunits are synthesized at the correct location and in stoichiometric ratios to prevent unassembled protein products from ge...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-04-0222
更新日期:2015-08-15 00:00:00
abstract::Mutations in the mitochondrial cardiolipin (CL) transacylase, tafazzin (Taz1p), result in the X-linked cardioskeletal myopathy, Barth syndrome (BTHS). The mitochondria of BTHS patients exhibit variable respiratory defects and abnormal cristae ultrastructure. The biochemical basis for these observations is unknown. In ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-09-0896
更新日期:2008-12-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Using cDNA microarrays to characterize patterns of gene expression in HCC, we found consistent differences between the expression patterns in HCC compared with those seen in nontumor liver tissues. The expression patterns in HCC were also readily di...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.02-02-0023
更新日期:2002-06-01 00:00:00
abstract::Anchorage dependence of cell growth, which is mediated by multiple integrin-regulated signaling pathways, is a key defense against cancer metastasis. Detachment of cells from the extracellular matrix triggers caveolin-1-dependent internalization of lipid raft components, which mediates suppression of Rho GTPases, Erk,...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-04-0361
更新日期:2011-09-01 00:00:00
abstract::ARL4D is a developmentally regulated member of the ADP-ribosylation factor/ARF-like protein (ARF/ARL) family of Ras-related GTPases. Although the primary structure of ARL4D is very similar to that of other ARF/ARL molecules, its function remains unclear. Cytohesin-2/ARF nucleotide-binding-site opener (ARNO) is a guani...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e07-02-0149
更新日期:2007-11-01 00:00:00
abstract::The TOR kinases are conserved negative regulators of autophagy in response to nutrient conditions, but the signaling mechanisms are poorly understood. Here we describe a complex containing the protein kinase Atg1 and the phosphoprotein Atg13 that functions as a critical component of this regulation in Drosophila. We s...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-12-1250
更新日期:2009-04-01 00:00:00
abstract::Phospholipase Ds (PLDs) are regulated enzymes that generate phosphatidic acid (PA), a putative second messenger implicated in the regulation of vesicular trafficking and cytoskeletal reorganization. Mast cells, when stimulated with antigen, show a dramatic alteration in their cytoskeleton and also release their secret...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e02-04-0213
更新日期:2002-10-01 00:00:00
abstract::Astrocytes in neuron-free cultures typically lack processes, although they are highly process-bearing in vivo. We show that basic fibroblast growth factor (bFGF) induces cultured astrocytes to grow processes and that Ras family GTPases mediate these morphological changes. Activated alleles of rac1 and rhoA blocked and...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.10.5.1665
更新日期:1999-05-01 00:00:00
abstract::Motility, chemotaxis, and the acrosome reaction of animal sperm are all regulated by cyclic nucleotides and protein phosphorylation. One of the cyclic AMP-dependent protein kinase (PKA) substrates in sea urchin sperm is a member of the phosphodiesterase (PDE) family. The molecular identity and in vivo function of this...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e05-08-0820
更新日期:2006-01-01 00:00:00
abstract::The TAM receptor protein tyrosine kinases Tyro3, Axl, and Mer play important roles in macrophage function. We investigated the roles of the TAM receptors in mediating the induction of hepatocyte growth factor (HGF) during the interaction of macrophages with apoptotic cells. Mer-specific neutralizing antibody, small in...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E12-01-0029
更新日期:2012-08-01 00:00:00
abstract::Insulin regulates glucose uptake into fat and muscle by modulating the distribution of the GLUT4 glucose transporter between the surface and interior of cells. The GLUT4 trafficking pathway overlaps with the general endocytic recycling pathway, but the degree and functional significance of the overlap are not known. I...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e02-02-0071
更新日期:2002-07-01 00:00:00
abstract::We provide guidelines for using statistical methods to analyze the types of experiments reported in cellular and molecular biology journals such as Molecular Biology of the Cell. Our aim is to help experimentalists use these methods skillfully, avoid mistakes, and extract the maximum amount of information from their l...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-02-0076
更新日期:2019-06-01 00:00:00
abstract::The BNIP-2 and Cdc42GAP homology (BCH) domain is a novel regulator for Rho GTPases, but its impact on p50-Rho GTPase-activating protein (p50RhoGAP or Cdc42GAP) in cells remains elusive. Here we show that deletion of the BCH domain from p50RhoGAP enhanced its GAP activity and caused drastic cell rounding. Introducing c...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E09-05-0408
更新日期:2010-09-15 00:00:00
abstract::A novel gene, prom-1, was isolated in a screen for Caenorhabditis elegans mutants with increased apoptosis in the germline. prom-1 encodes an F-box protein with limited homology to the putative human tumor suppressor FBXO47. Mutations in the prom-1 locus cause a strong reduction in bivalent formation, which results in...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e07-03-0243
更新日期:2007-12-01 00:00:00