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

Abstract:

: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.

journal_name

Mol Biol Cell

authors

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

doi

10.1091/mbc.E15-09-0671

subject

Has Abstract

pub_date

2015-12-15 00:00:00

pages

4700-17

issue

25

eissn

1059-1524

issn

1939-4586

pii

mbc.E15-09-0671

journal_volume

26

pub_type

杂志文章
  • Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes.

    abstract::Dysregulated hepatic cholesterol homeostasis with free cholesterol accumulation in the liver is relevant to the pathogenesis of nonalcoholic steatohepatitis, contributing to the chronicity of liver toxicity. Here we examined the effect of free cholesterol accumulation on the morphology and biochemical properties of li...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-10-0730

    authors: Makino A,Hullin-Matsuda F,Murate M,Abe M,Tomishige N,Fukuda M,Yamashita S,Fujimoto T,Vidal H,Lagarde M,Delton I,Kobayashi T

    更新日期:2016-11-01 00:00:00

  • Distribution and transport of cholesterol in Caenorhabditis elegans.

    abstract::Cholesterol transport is an essential process in all multicellular organisms. In this study we applied two recently developed approaches to investigate the distribution and molecular mechanisms of cholesterol transport in Caenorhabditis elegans. The distribution of cholesterol in living worms was studied by imaging it...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.6.1725

    authors: Matyash V,Geier C,Henske A,Mukherjee S,Hirsh D,Thiele C,Grant B,Maxfield FR,Kurzchalia TV

    更新日期:2001-06-01 00:00:00

  • Distinct roles for the AAA ATPases NSF and p97 in the secretory pathway.

    abstract::NSF and p97 are related AAA proteins implicated in membrane trafficking and organelle biogenesis. p97 is also involved in pathways that lead to ubiquitin-dependent proteolysis, including ER-associated degradation (ERAD). In this study, we have used dominant interfering ATP-hydrolysis deficient mutants (NSF(E329Q) and ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-02-0097

    authors: Dalal S,Rosser MF,Cyr DM,Hanson PI

    更新日期:2004-02-01 00:00:00

  • Overexpression of a novel rho family GTPase, RacC, induces unusual actin-based structures and positively affects phagocytosis in Dictyostelium discoideum.

    abstract::Rho family proteins have been implicated in regulating various cellular processes, including actin cytoskeleton organization, endocytosis, cell cycle, and gene expression. In this study, we analyzed the function of a novel Dictyostelium discoideum Rho family protein (RacC). A cell line was generated that conditionally...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.10.2891

    authors: Seastone DJ,Lee E,Bush J,Knecht D,Cardelli J

    更新日期:1998-10-01 00:00:00

  • In vitro assembly of coiled bodies in Xenopus egg extract.

    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

    authors: Bauer DW,Murphy C,Wu Z,Wu CH,Gall JG

    更新日期:1994-06-01 00:00:00

  • Actin cross-linking proteins cortexillin I and II are required for cAMP signaling during Dictyostelium chemotaxis and development.

    abstract::Starvation induces Dictyostelium amoebae to secrete cAMP, toward which other amoebae stream, forming multicellular mounds that differentiate and develop into fruiting bodies containing spores. We find that the double deletion of cortexillin (ctx) I and II alters the actin cytoskeleton and substantially inhibits all mo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-09-0764

    authors: Shu S,Liu X,Kriebel PW,Daniels MP,Korn ED

    更新日期:2012-01-01 00:00:00

  • Coupling to substrate adhesions drives the maturation of muscle stress fibers into myofibrils within cardiomyocytes.

    abstract::Forces generated by heart muscle contraction must be balanced by adhesion to the extracellular matrix (ECM) and to other cells for proper heart function. Decades of data have suggested that cell-ECM adhesions are important for sarcomere assembly. However, the relationship between cell-ECM adhesions and sarcomeres asse...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-11-0652

    authors: Taneja N,Neininger AC,Burnette DT

    更新日期:2020-06-01 00:00:00

  • XB130/Tks5 scaffold protein interaction regulates Src-mediated cell proliferation and survival.

    abstract::The scaffold protein XB130 regulates cell growth, survival, and migration. Yeast two-hybrid screening suggests that XB130 interacts with another scaffold protein, Tks5. We hypothesized that XB130 and Tks5 form a macromolecular complex to mediate signal transduction cascades for the regulation of cell growth and surviv...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-07-0483

    authors: Moodley S,Hui Bai X,Kapus A,Yang B,Liu M

    更新日期:2015-12-01 00:00:00

  • Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and phosphorylates Drosophila Cdc2 in vitro.

    abstract::Cdc2 kinase activity is required for triggering entry into mitosis in all known eukaryotes. Elaborate mechanisms have evolved for regulating Cdc2 activity so that mitosis occurs in a timely manner, when preparations for its execution are complete. In Schizosaccharomyces pombe, Wee1 and a related Mik1 kinase are Cdc2-i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.6.10.1333

    authors: Campbell SD,Sprenger F,Edgar BA,O'Farrell PH

    更新日期:1995-10-01 00:00:00

  • Alg13p, the catalytic subunit of the endoplasmic reticulum UDP-GlcNAc glycosyltransferase, is a target for proteasomal degradation.

    abstract::The second step of dolichol-linked oligosaccharide synthesis in the N-linked glycosylation pathway at the endoplasmic reticulum (ER) membrane is catalyzed by an unusual hetero-oligomeric UDP-N-acetylglucosamine transferase that in most eukaryotes is comprised of at least two subunits, Alg13p and Alg14p. Alg13p is the ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-10-1077

    authors: Averbeck N,Gao XD,Nishimura S,Dean N

    更新日期:2008-05-01 00:00:00

  • In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements.

    abstract::In neurons certain mRNA transcripts are transported to synapses through mechanisms that are not fully understood. Here we report that the heterogeneous nuclear ribonucleoprotein CBF-A (CArG Box binding Factor A) facilitates dendritic transport and localization of activity-regulated cytoskeleton-associated protein (Arc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-11-0904

    authors: Raju CS,Fukuda N,López-Iglesias C,Göritz C,Visa N,Percipalle P

    更新日期:2011-06-01 00:00:00

  • The secretory pathway at 50: a golden anniversary for some momentous grains of silver.

    abstract::The secretory pathway along which newly synthesized secretory and membrane proteins traffic through the cell was revealed in two articles published 50 years ago. This discovery was the culmination of decades of effort to unite the power of biochemical and morphological methodologies in order to elucidate the dynamic n...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-07-0508

    authors: Matlin KS,Caplan MJ

    更新日期:2017-01-15 00:00:00

  • S100A4 regulates macrophage chemotaxis.

    abstract::S100A4, a member of the S100 family of Ca(2+)-binding proteins, is directly involved in tumor metastasis. In addition to its expression in tumor cells, S100A4 is expressed in normal cells and tissues, including fibroblasts and cells of the immune system. To examine the contribution of S100A4 to normal physiology, we e...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-07-0609

    authors: Li ZH,Dulyaninova NG,House RP,Almo SC,Bresnick AR

    更新日期:2010-08-01 00:00:00

  • Enteropathogenic Escherichia coli subverts phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate upon epithelial cell infection.

    abstract::Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] are phosphoinositides (PIs) present in small amounts in the inner leaflet of the plasma membrane (PM) lipid bilayer of host target cells. They are thought to modulate the activity of proteins involved in en...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-05-0516

    authors: Sason H,Milgrom M,Weiss AM,Melamed-Book N,Balla T,Grinstein S,Backert S,Rosenshine I,Aroeti B

    更新日期:2009-01-01 00:00:00

  • Endoplasmic reticulum stress regulation of the Kar2p/BiP chaperone alleviates proteotoxicity via dual degradation pathways.

    abstract::The unfolded protein response (UPR) monitors and maintains protein homeostasis in the endoplasmic reticulum (ER). In budding yeast, the UPR is a transcriptional regulatory pathway that is quiescent under normal conditions. Under conditions of acute ER stress, activation of UPR targets is essential for cell viability. ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-04-0297

    authors: Hsu CL,Prasad R,Blackman C,Ng DT

    更新日期:2012-02-01 00:00:00

  • Molecular mechanisms underlying cellular effects of human MEK1 mutations.

    abstract::Terminal regions of Drosophila embryos are patterned by signaling through ERK, which is genetically deregulated in multiple human diseases. Quantitative studies of terminal patterning have been recently used to investigate gain-of-function variants of human MEK1, encoding the MEK kinase that directly activates ERK by ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-10-0625

    authors: Marmion RA,Yang L,Goyal Y,Jindal GA,Wetzel JL,Singh M,Schüpbach T,Shvartsman SY

    更新日期:2021-01-21 00:00:00

  • The HIF target ATG9A is essential for epithelial barrier function and tight junction biogenesis.

    abstract::Intestinal epithelial cells (IECs) exist in a metabolic state of low oxygen tension termed "physiologic hypoxia." An important factor in maintaining intestinal homeostasis is the transcription factor hypoxia-inducible factor (HIF), which is stabilized under hypoxic conditions and mediates IEC homeostatic responses to ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-05-0291

    authors: Dowdell AS,Cartwright IM,Goldberg MS,Kostelecky R,Ross T,Welch N,Glover LE,Colgan SP

    更新日期:2020-09-15 00:00:00

  • The 90-kDa heat shock protein stabilizes the polysomal ribonuclease 1 mRNA endonuclease to degradation by the 26S proteasome.

    abstract::The polysomal ribonuclease 1 (PMR1) mRNA endonuclease forms a selective complex with its translating substrate mRNAs where it is activated to initiate mRNA decay. Previous work showed tyrosine phosphorylation is required for PMR1 targeting to this polysome-bound complex, and it identified c-Src as the responsible kina...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-08-0774

    authors: Peng Y,Liu X,Schoenberg DR

    更新日期:2008-02-01 00:00:00

  • The two SAS-6 homologs in Tetrahymena thermophila have distinct functions in basal body assembly.

    abstract::Cilia and flagella are structurally and functionally conserved organelles present in basal as well as higher eukaryotes. The assembly of cilia requires a microtubule based scaffold called a basal body. The ninefold symmetry characteristic of basal bodies and the structurally similar centriole is organized around a hub...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-08-0838

    authors: Culver BP,Meehl JB,Giddings TH Jr,Winey M

    更新日期:2009-03-01 00:00:00

  • Dictyostelium EB1 is a genuine centrosomal component required for proper spindle formation.

    abstract::EB1 proteins are ubiquitous microtubule-associated proteins involved in microtubule search and capture, regulation of microtubule dynamics, cell polarity, and chromosome stability. We have cloned a complete cDNA of Dictyostelium EB1 (DdEB1), the largest known EB1 homolog (57 kDa). Immunofluorescence analysis and expre...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-01-0054

    authors: Rehberg M,Gräf R

    更新日期:2002-07-01 00:00:00

  • The zinc transporter ZnT3 interacts with AP-3 and it is preferentially targeted to a distinct synaptic vesicle subpopulation.

    abstract::Synaptic vesicles (SV) are generated by two different mechanisms, one AP-2 dependent and one AP-3 dependent. It has been uncertain, however, whether these mechanisms generate SV that differ in molecular composition. We explored this hypothesis by analyzing the targeting of ZnT3 and synaptophysin both to PC12 synaptic-...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-06-0401

    authors: Salazar G,Love R,Werner E,Doucette MM,Cheng S,Levey A,Faundez V

    更新日期:2004-02-01 00:00:00

  • E. E. Just Award lecture.

    abstract::What started as a game of discovery for a child with a chemistry set has resulted in a lifetime of fulfillment and dedication to science. It is deeply rewarding to continuously let my curiosity ask questions for which there are no known answers. Equally rewarding has been the opportunity to mentor young students and p...

    journal_title:Molecular biology of the cell

    pub_type: 传,历史文章,杂志文章

    doi:10.1091/mbc.E13-07-0407

    authors: Garcia JV

    更新日期:2013-11-01 00:00:00

  • Budding yeast Dma1 and Dma2 participate in regulation of Swe1 levels and localization.

    abstract::Timely down-regulation of the evolutionarily conserved protein kinase Swe1 plays an important role in cell cycle control, as Swe1 can block nuclear division through inhibitory phosphorylation of the catalytic subunit of cyclin-dependent kinase. In particular, Swe1 degradation is important for budding yeast cell surviv...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-02-0127

    authors: Raspelli E,Cassani C,Lucchini G,Fraschini R

    更新日期:2011-07-01 00:00:00

  • Compositional complexity of rods and rings.

    abstract::Rods and rings (RRs) are large linear- or circular-shaped structures typically described as polymers of IMPDH (inosine monophosphate dehydrogenase). They have been observed across a wide variety of cell types and species and can be induced to form by inhibitors of IMPDH. RRs are thought to play a role in the regulatio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-05-0274

    authors: Schiavon CR,Griffin ME,Pirozzi M,Parashuraman R,Zhou W,Jinnah HA,Reines D,Kahn RA

    更新日期:2018-09-15 00:00:00

  • Two related kinesins, klp5+ and klp6+, foster microtubule disassembly and are required for meiosis in fission yeast.

    abstract::The kinesin superfamily of microtubule motor proteins is important in many cellular processes, including mitosis and meiosis, vesicle transport, and the establishment and maintenance of cell polarity. We have characterized two related kinesins in fission yeast, klp5+ and klp6+,, that are amino-terminal motors of the K...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.12.3919

    authors: West RR,Malmstrom T,Troxell CL,McIntosh JR

    更新日期:2001-12-01 00:00:00

  • A novel pathway of rapid TLR-triggered activation of integrin-dependent leukocyte adhesion that requires Rap1 GTPase.

    abstract::Rapid β2-integrin activation is indispensable for leukocyte adhesion and recruitment to sites of infection and is mediated by chemokine- or P-selectin glycoprotein ligand-1-induced inside-out signaling. Here we uncovered a novel pathway for rapid activation of integrin-dependent leukocyte adhesion, triggered by toll-l...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-04-0867

    authors: Chung KJ,Mitroulis I,Wiessner JR,Zheng YY,Siegert G,Sperandio M,Chavakis T

    更新日期:2014-10-01 00:00:00

  • A dependent pathway of cytoplasmic polyadenylation reactions linked to cell cycle control by c-mos and CDK1 activation.

    abstract::During oocyte maturation and early development, mRNAs receive poly(A) in the cytoplasm at distinct times relative to one another and to the cell cycle. These cytoplasmic polyadenylation reactions do not occur during oogenesis, but begin during oocyte maturation and continue throughout early development. In this report...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.8.8.1633

    authors: Ballantyne S,Daniel DL Jr,Wickens M

    更新日期:1997-08-01 00:00:00

  • The lipid-anchored ectodomain of influenza virus hemagglutinin (GPI-HA) is capable of inducing nonenlarging fusion pores.

    abstract::GPI-linked hemagglutinin (GPI-HA) of influenza virus was thought to induce hemifusion without pore formation. Cells expressing either HA or GPI-HA were bound to red blood cells, and their fusion was compared by patch-clamp capacitance measurements and fluorescence microscopy. It is now shown that under more optimal fu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.4.1143

    authors: Markosyan RM,Cohen FS,Melikyan GB

    更新日期:2000-04-01 00:00:00

  • Asymmetric localization of calpain 2 during neutrophil chemotaxis.

    abstract::Chemoattractants induce neutrophil polarization through localized polymerization of F-actin at the leading edge. The suppression of rear and lateral protrusions is required for efficient chemotaxis and involves the temporal and spatial segregation of signaling molecules. We have previously shown that the intracellular...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-09-0876

    authors: Nuzzi PA,Senetar MA,Huttenlocher A

    更新日期:2007-03-01 00:00:00

  • Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis.

    abstract::Meiosis involves two successive rounds of chromosome segregation without an intervening S phase. Exit from meiosis I is distinct from mitotic exit, in that replication origins are not licensed by Mcm2-7 chromatin binding, but spindle disassembly occurs during a transient interphase-like state before meiosis II. The ab...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-11-0825

    authors: Hua H,Namdar M,Ganier O,Gregan J,Méchali M,Kearsey SE

    更新日期:2013-03-01 00:00:00