Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion.


:Hedgehog (Hh) is a secreted morphogen involved in both short- and long-range signaling necessary for tissue patterning during development. It is unclear how this dually lipidated protein is transported over a long range in the aqueous milieu of interstitial spaces. We previously showed that the long-range signaling of Hh requires its oligomerization. Here we show that Hh is secreted in the form of exovesicles. These are derived by the endocytic delivery of cell surface Hh to multivesicular bodies (MVBs) via an endosomal sorting complex required for transport (ECSRT)-dependent process. Perturbations of ESCRT proteins have a selective effect on long-range Hh signaling in Drosophila wing imaginal discs. Of importance, oligomerization-defective Hh is inefficiently incorporated into exovesicles due to its poor endocytic delivery to MVBs. These results provide evidence that nanoscale organization of Hh regulates the secretion of Hh on ESCRT-derived exovesicles, which in turn act as a vehicle for long-range signaling.


Mol Biol Cell


Parchure A,Vyas N,Ferguson C,Parton RG,Mayor S




Has Abstract


2015-12-15 00:00:00














  • Synthetic lethal interaction of the mitochondrial phosphatidylethanolamine biosynthetic machinery with the prohibitin complex of Saccharomyces cerevisiae.

    abstract::The majority of mitochondrial phosphatidylethanolamine (PtdEtn), a phospholipid essential for aerobic growth of yeast cells, is synthesized by phosphatidylserine decarboxylase 1 (Psd1p) in the inner mitochondrial membrane (IMM). To identify components that become essential when the level of mitochondrial PtdEtn is dec...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Birner R,Nebauer R,Schneiter R,Daum G

    更新日期:2003-02-01 00:00:00

  • Septins, under Cla4p regulation, and the chitin ring are required for neck integrity in budding yeast.

    abstract::CLA4, encoding a protein kinase of the PAK type, and CDC11, encoding a septin, were isolated in a screen for synthetic lethality with CHS3, which encodes the chitin synthase III catalytic moiety. Although Ste20p shares some essential function with Cla4p, it did not show synthetic lethality with Chs3p. cla4 and cdc11 m...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Schmidt M,Varma A,Drgon T,Bowers B,Cabib E

    更新日期:2003-05-01 00:00:00

  • GRASP depletion-mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin.

    abstract::The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids. To perform these functions, the Golgi forms a multilayer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners. Depletion of GRASP proteins disru...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Ahat E,Xiang Y,Zhang X,Bekier ME 2nd,Wang Y

    更新日期:2019-03-15 00:00:00

  • Regulated phosphorylation of budding yeast's essential myosin V heavy chain, Myo2p.

    abstract::The tail of the yeast myosin V encoded by Myo2p is known to bind several receptors for cargo delivery along polarized actin cables. However, it is not known how Myo2p activity is regulated or how it selects between cargoes. Here we show that Myo2p is reversibly phosphorylated in vivo. A short peptide at the N-terminal...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Legesse-Miller A,Zhang S,Santiago-Tirado FH,Van Pelt CK,Bretscher A

    更新日期:2006-04-01 00:00:00

  • The TAM-family receptor Mer mediates production of HGF through the RhoA-dependent pathway in response to apoptotic cells.

    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


    authors: Park HJ,Baen JY,Lee YJ,Choi YH,Kang JL

    更新日期:2012-08-01 00:00:00

  • The role of the Src homology domains in morphological transformation by v-src.

    abstract::The Src homology (SH2 and SH3) domains of v-Src are required for transformation of Rat-2 cells and for wild-type (morphr) transformation of chicken embryo fibroblasts (CEFs). We report herein that the N-terminal domains of v-Src, when expressed in trans, cannot complement the transformation defect of a deletion mutant...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Tian M,Martin GS

    更新日期:1997-07-01 00:00:00

  • Sep7 is essential to modify septin ring dynamics and inhibit cell separation during Candida albicans hyphal growth.

    abstract::When Candida albicans yeast cells receive the appropriate stimulus, they switch to hyphal growth, characterized by continuous apical elongation and the inhibition of cell separation. The molecular basis of this inhibition is poorly known, despite its crucial importance for hyphal development. In C. albicans, septins a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: González-Novo A,Correa-Bordes J,Labrador L,Sánchez M,Vázquez de Aldana CR,Jiménez J

    更新日期:2008-04-01 00:00:00

  • Microtubule flux mediates poleward motion of acentric chromosome fragments during meiosis in insect spermatocytes.

    abstract::We applied a combination of laser microsurgery and quantitative polarization microscopy to study kinetochore-independent forces that act on chromosome arms during meiosis in crane fly spermatocytes. When chromosome arms located within one of the half-spindles during prometa- or metaphase were cut with the laser, the a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: LaFountain JR Jr,Oldenbourg R,Cole RW,Rieder CL

    更新日期:2001-12-01 00:00:00

  • Yeast cycloheximide-resistant crl mutants are proteasome mutants defective in protein degradation.

    abstract::In 1988 McCusker and Haber generated a series of mutants which are resistant to the minimum inhibitory concentration of the protein synthesis inhibitor cycloheximide. These cycloheximide-resistant, temperature-sensitive (crl) mutants, in addition, exhibited other pleiotropic phenotypes, e.g., incorrect response to sta...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Gerlinger UM,Gückel R,Hoffmann M,Wolf DH,Hilt W

    更新日期:1997-12-01 00:00:00

  • Mam33 promotes cytochrome c oxidase subunit I translation in Saccharomyces cerevisiae mitochondria.

    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


    authors: Roloff GA,Henry MF

    更新日期:2015-08-15 00:00:00

  • In vitro BioID: mapping the CENP-A microenvironment with high temporal and spatial resolution.

    abstract::The centromere is located at the primary constriction of condensed chromosomes where it acts as a platform regulating chromosome segregation. The histone H3 variant CENP-A is the foundation for kinetochore formation. CENP-A directs the formation of a highly dynamic molecular neighborhood whose temporal characterizatio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Remnant L,Booth DG,Vargiu G,Spanos C,Kerr ARW,Earnshaw WC

    更新日期:2019-05-15 00:00:00

  • The putative G protein-coupled receptor GrlD mediates extracellular polyphosphate sensing in Dictyostelium discoideum.

    abstract::Five or more orthophosphates bound together by high-energy phosphoanhydride bonds are highly ubiquitous inorganic molecules called polyphosphate. Polyphosphate acts as a signaling molecule eliciting a number of responses in eukaryotic cells, but the mechanisms mediating these effects are poorly understood. Proliferati...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Suess PM,Tang Y,Gomer RH

    更新日期:2019-04-15 00:00:00

  • Mechanistic insights into actin-driven polarity site movement in yeast.

    abstract::Directed cell growth or migration are critical for the development and function of many eukaryotic cells. These cells develop a dynamic "front" (also called "polarity site") that can change direction. Polarity establishment involves autocatalytic accumulation of polarity regulators, including the conserved Rho-family ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Ghose D,Lew D

    更新日期:2020-05-01 00:00:00

  • Mechanisms of invasion and motility of high-grade gliomas in the brain.

    abstract::High-grade gliomas are especially difficult tumors to treat due to their invasive behavior. This has led to extensive research focusing on arresting glioma cell migration. Cell migration involves the sensing of a migratory cue, followed by polarization in the direction of the cue, and reorganization of the actin cytos...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章,评审


    authors: Mair DB,Ames HM,Li R

    更新日期:2018-10-15 00:00:00

  • Different subcellular localization of Saccharomyces cerevisiae HMG-CoA reductase isozymes at elevated levels corresponds to distinct endoplasmic reticulum membrane proliferations.

    abstract::In all eucaryotic cell types analyzed, proliferations of the endoplasmic reticulum (ER) can be induced by increasing the levels of certain integral ER proteins. One of the best characterized of these proteins is HMG-CoA reductase, which catalyzes the rate-limiting step in sterol biosynthesis. We have investigated the ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Koning AJ,Roberts CJ,Wright RL

    更新日期:1996-05-01 00:00:00

  • Defects in structural integrity of ergosterol and the Cdc50p-Drs2p putative phospholipid translocase cause accumulation of endocytic membranes, onto which actin patches are assembled in yeast.

    abstract::Specific changes in membrane lipid composition are implicated in actin cytoskeletal organization, vesicle formation, and control of cell polarity. Cdc50p, a membrane protein in the endosomal/trans-Golgi network compartments, is a noncatalytic subunit of Drs2p, which is implicated in translocation of phospholipids acro...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Kishimoto T,Yamamoto T,Tanaka K

    更新日期:2005-12-01 00:00:00

  • Cdk1-dependent phosphoinhibition of a formin-F-BAR interaction opposes cytokinetic contractile ring formation.

    abstract::In Schizosaccharomyces pombe, cytokinesis requires the assembly and constriction of an actomyosin-based contractile ring (CR). A single essential formin, Cdc12, localizes to the cell middle upon mitotic onset and nucleates the F-actin of the CR. Cdc12 medial recruitment is mediated in part by its direct binding to the...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Willet AH,Bohnert KA,Gould KL

    更新日期:2018-03-15 00:00:00

  • An RNA interference screen identifies a novel regulator of target of rapamycin that mediates hypoxia suppression of translation in Drosophila S2 cells.

    abstract::In addition to its central role in energy production, oxygen has pervasive regulatory actions. Hypoxia (oxygen limitation) triggers the shutdown of major cellular processes, including gene expression. We carried out a genome-wide RNA interference (RNAi) screen in Drosophila S2 cells for functions required to down-regu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Lee SJ,Feldman R,O'Farrell PH

    更新日期:2008-10-01 00:00:00

  • A myopathy-linked desmin mutation perturbs striated muscle actin filament architecture.

    abstract::Desmin interacts with nebulin establishing a direct link between the intermediate filament network and sarcomeres at the Z-discs. Here, we examined a desmin mutation, E245D, that is located within the coil IB (nebulin-binding) region of desmin and that has been reported to cause human cardiomyopathy and skeletal muscl...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Conover GM,Henderson SN,Gregorio CC

    更新日期:2009-02-01 00:00:00

  • Amyloid-β oligomers induce tau-independent disruption of BDNF axonal transport via calcineurin activation in cultured hippocampal neurons.

    abstract::Disruption of fast axonal transport (FAT) is an early pathological event in Alzheimer's disease (AD). Soluble amyloid-β oligomers (AβOs), increasingly recognized as proximal neurotoxins in AD, impair organelle transport in cultured neurons and transgenic mouse models. AβOs also stimulate hyperphosphorylation of the ax...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Ramser EM,Gan KJ,Decker H,Fan EY,Suzuki MM,Ferreira ST,Silverman MA

    更新日期:2013-08-01 00:00:00

  • cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor.

    abstract::MPM-2 antigens, a discrete set of phosphoproteins that contain similar phosphoepitopes recognized by the monoclonal antibody MPM-2, are phosphorylated during M-phase induction. Our previous studies suggested that certain MPM-2 antigens are involved in the appearance of maturation-promoting factor (MPF) activity. Becau...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Kuang J,Ashorn CL,Gonzalez-Kuyvenhoven M,Penkala JE

    更新日期:1994-02-01 00:00:00

  • Brush border protocadherin CDHR2 promotes the elongation and maximized packing of microvilli in vivo.

    abstract::Transporting epithelial cells optimize their morphology for solute uptake by building an apical specialization: a dense array of microvilli that serves to increase membrane surface area. In the intestinal tract, individual cells build thousands of microvilli, which pack tightly to form the brush border. Recent studies...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Pinette JA,Mao S,Millis BA,Krystofiak ES,Faust JJ,Tyska MJ

    更新日期:2019-01-01 00:00:00

  • The GTPase SPAG-1 orchestrates meiotic program by dictating meiotic resumption and cytoskeleton architecture in mouse oocytes.

    abstract::In mammals, a finite population of oocytes is generated during embryogenesis, and proper oocyte meiotic divisions are crucial for fertility. Sperm-associated antigen 1 (SPAG-1) has been implicated in infertility and tumorigenesis; however, its relevance in cell cycle programs remains rudimentary. Here we explore a nov...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Huang C,Wu D,Khan FA,Jiao X,Guan K,Huo L

    更新日期:2016-06-01 00:00:00

  • Synaptic vesicles form by budding from tubular extensions of sorting endosomes in PC12 cells.

    abstract::The putative role of sorting early endosomes (EEs) in synaptic-like microvesicle (SLMV) formation in the neuroendocrine PC12 cell line was investigated by quantitative immunoelectron microscopy. By BSA-gold internalization kinetics, four distinct endosomal subcompartments were distinguished: primary endocytic vesicles...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: de Wit H,Lichtenstein Y,Geuze HJ,Kelly RB,van der Sluijs P,Klumperman J

    更新日期:1999-12-01 00:00:00

  • Characterizing the roles of Met31 and Met32 in coordinating Met4-activated transcription in the absence of Met30.

    abstract::Yeast sulfur metabolism is transcriptionally regulated by the activator Met4. Met4 lacks DNA-binding ability and relies on interactions with Met31 and Met32, paralogous proteins that bind the same cis-regulatory element, to activate its targets. Although Met31 and Met32 are redundant for growth in the absence of methi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Carrillo E,Ben-Ari G,Wildenhain J,Tyers M,Grammentz D,Lee TA

    更新日期:2012-05-01 00:00:00

  • Fifty years of microtubule sliding in cilia.

    abstract::Motility of cilia (also known as flagella in some eukaryotes) is based on axonemal doublet microtubule sliding that is driven by the dynein molecular motors. Dyneins are organized into intricately patterned inner and outer rows of arms, whose collective activity is to produce inter-microtubule movement. However, to ge...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: King SM,Sale WS

    更新日期:2018-03-15 00:00:00

  • NGF controls dendrite development in hippocampal neurons by binding to p75NTR and modulating the cellular targets of Notch.

    abstract::Notch and neurotrophins control neuronal shape, but it is not known whether their signaling pathways intersect. Here we report results from hippocampal neuronal cultures that are in support of this possibility. We found that low cell density or blockade of Notch signaling by a soluble Delta-Fc ligand decreased the mRN...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Salama-Cohen P,Arévalo MA,Meier J,Grantyn R,Rodríguez-Tébar A

    更新日期:2005-01-01 00:00:00

  • Structural organization of nuclear lamins A, C, B1, and B2 revealed by superresolution microscopy.

    abstract::The nuclear lamina is a key structural element of the metazoan nucleus. However, the structural organization of the major proteins composing the lamina is poorly defined. Using three-dimensional structured illumination microscopy and computational image analysis, we characterized the supramolecular structures of lamin...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Shimi T,Kittisopikul M,Tran J,Goldman AE,Adam SA,Zheng Y,Jaqaman K,Goldman RD

    更新日期:2015-11-05 00:00:00

  • A novel yeast screen for mitotic arrest mutants identifies DOC1, a new gene involved in cyclin proteolysis.

    abstract::B-type cyclins are rapidly degraded at the transition between metaphase and anaphase and their ubiquitin-mediated proteolysis is required for cells to exit mitosis. We used a novel enrichment to isolate new budding mutants that arrest the cell cycle in mitosis. Most of these mutants lie in the CDC16, CDC23, and CDC27 ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Hwang LH,Murray AW

    更新日期:1997-10-01 00:00:00

  • Phosphatidic acid induces ligand-independent epidermal growth factor receptor endocytic traffic through PDE4 activation.

    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


    authors: Norambuena A,Metz C,Jung JE,Silva A,Otero C,Cancino J,Retamal C,Valenzuela JC,Soza A,González A

    更新日期:2010-08-15 00:00:00