Hsc70 is required for endocytosis and clathrin function in Drosophila

By screening for Drosophila mutants exhibiting aberrant bride of sevenless (Boss) staining patterns on eye imaginal disc epithelia, we have recovered a point mutation in Hsc70-4, the closest homologue to bovine clathrin uncoating ATPase. Although the mutant allele was lethal, analysis of mutant clones generated by FLP/FRT recombination demonstrated that the Sevenless-mediated internalization of Boss was blocked in mutant Hsc70-4 eye disc epithelial cells. Endocytosis of other probes was also greatly inhibited in larval Garland cells. Immunostaining and EM analysis of the mutant cells revealed disruptions in the organization of endosomal/lysosomal compartments, including a substantial reduction in the number of clathrin-coated structures in Garland cells. The Hsc70-4 mutation also interacted genetically with a dominant-negative mutant of dynamin, a gene required for the budding of clathrin-coated vesicles (CCVs). Consistent with these phenotypes, recombinant mutant Hsc70 proteins exhibited diminished clathrin uncoating activity in vitro. Together, these data provide genetic support for the long-suspected role of Hsc70 in clathrin-mediated endocytosis, at least in part by inhibiting the uncoating of CCVs.

• Publication year

  2002

• Venue

  Journal of Cell Biology

• Publication date

  2002-11-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200205086PMID 12427870PMCID 2173062
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Dynamin GTPase domain mutants block endocytic vesicle formation at morphologically distinct stages.

  2001cited by this paper
• Sorting of Mannose 6-Phosphate Receptors Mediated by the GGAs

  2001cited by this paper
• Distribution and Function of Ap-1 Clathrin Adaptor Complexes in Polarized Epithelial Cells

  2001cited by this paper
• Caenorhabditis elegans auxilin: a J-domain protein essential for clathrin-mediated endocytosis in vivo

  2001cited by this paper
• Drosophila Hsc70-4 is critical for neurotransmitter exocytosis in vivo.

  2001influential reference
• Dominant-Interfering Hsc70 Mutants Disrupt Multiple Stages of the Clathrin-Coated Vesicle Cycle in Vivo

  2001influential reference
• Uncoating of clathrin-coated vesicles in presynaptic terminals: roles for Hsc70 and auxilin.

  2001cited by this paper
• RME-8, a conserved J-domain protein, is required for endocytosis in Caenorhabditis elegans.

  2001cited by this paper
• Identification of the universal cofactor (auxilin 2) in clathrin coat dissociation.

  2000cited by this paper
• Garrotes, Springs, Ratchets, and Whips: Putting Dynamin Models to the Test

  2000cited by this paper
• Drosophila atonal controls photoreceptor R8-specific properties and modulates both receptor tyrosine kinase and Hedgehog signalling.

  2000cited by this paper
• A yeast DNA J protein required for uncoating of clathrin-coated vesicles in vivo

  2000cited by this paper
• Gradient Formation of the TGF-b Homolog Dpp

  2000cited by this paper
• Gradient formation of the TGF-beta homolog Dpp.

  2000cited by this paper
• μ1A‐adaptin‐deficient mice: lethality, loss of AP‐1 binding and rerouting of mannose 6‐phosphate receptors

  2000cited by this paper
• Dynamin and its role in membrane fission.

  2000cited by this paper
• A Drosophila Clathrin Light-Chain Gene: Sequence, Mapping, and Absence of Neuronal Specialization

  1999cited by this paper
• A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells.

  1999cited by this paper
• Mutations in the heatshock cognate 70 protein (hsc4) modulate Notch signaling.

  1999influential reference
• High-resolution solution structure of the 18 kDa substrate-binding domain of the mammalian chaperone protein Hsc70.

  1999cited by this paper
• Spatial control of coated-pit dynamics in living cells

  1999cited by this paper
• The Stoned Proteins Regulate Synaptic Vesicle Recycling in the Presynaptic Terminal

  1999cited by this paper
• Genetic dissection of endocytic trafficking in Drosophila using a horseradish peroxidase-bride of sevenless chimera: hook is required for normal maturation of multivesicular endosomes.

  1999cited by this paper
• Investigation of the interaction between DnaK and DnaJ by surface plasmon resonance spectroscopy.

  1999cited by this paper
• The Hsp70 and Hsp60 chaperone machines.

  1998cited by this paper
• In Polarized MDCK Cells Basolateral Vesicles Arise from Clathrin-γ-adaptin–coated Domains on Endosomal Tubules

  1998cited by this paper
• ATP- and cytosol-dependent release of adaptor proteins from clathrin-coated vesicles: A dual role for Hsc70.

  1998cited by this paper
• Mechanism of clathrin basket dissociation: separate functions of protein domains of the DnaJ homologue auxilin

  1996influential reference
• A novel class of clathrin-coated vesicles budding from endosomes

  1996cited by this paper
• Mutations in the Drosophila hook gene inhibit endocytosis of the boss transmembrane ligand into multivesicular bodies

  1996cited by this paper
• Clathrin-independent pinocytosis is induced in cells overexpressing a temperature-sensitive mutant of dynamin

  1995cited by this paper
• Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death.

  1995cited by this paper
• Ectopic cyclin E expression induces premature entry into S phase and disrupts pattern formation in the Drosophila eye imaginal disc.

  1995cited by this paper
• Role of auxilin in uncoating clathrin-coated vesicles

  1995influential reference
• Receptor-mediated endocytosis is sensitive to antibodies against the uncoating ATPase (hsc70).

  1994cited by this paper
• Determination of neuronal cell fate: lessons from the R7 neuron of Drosophila.

  1994cited by this paper
• Expression of baculovirus P35 prevents cell death in Drosophila.

  1994cited by this paper
• Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.

  1993cited by this paper
• Analysis of genetic mosaics in developing and adult Drosophila tissues.

  1993influential reference
• The bride of sevenless and sevenless interaction: internalization of a transmembrane ligand.

  1992influential reference
• Multiple forms of dynamin are encoded by shibire, a Drosophila gene involved in endocytosis

  1991cited by this paper
• Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic

  1991cited by this paper
• Induction of cell fate in the Drosophila retina: the bride of sevenless protein is predicted to contain a large extracellular domain and seven transmembrane segments.

  1990cited by this paper
• Molecular and developmental characterization of the heat shock cognate 4 gene of Drosophila melanogaster

  1990influential reference
• The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin.

  1990cited by this paper
• The biogenesis of lysosomes.

  1989cited by this paper
• The locus elav of Drosophila melanogaster is expressed in neurons at all developmental stages.

  1988cited by this paper
• The ATPase core of a clathrin uncoating protein.

  1987cited by this paper
• Localization of the sevenless protein, a putative receptor for positional information, in the eye imaginal disc of Drosophila.

  1987influential reference
• Uncoating ATPase is a member of the 70 kilodalton family of stress proteins.

  1986cited by this paper
• The nucleotide sequence and the tissue-specific expression of Drosophila c-src.

  1985cited by this paper
• Cathepsin D precursors in clathrin-coated organelles from human fibroblasts

  1985cited by this paper
• An enzyme that removes clathrin coats: purification of an uncoating ATPase

  1984influential reference
• Reversible blockage of membrane retrieval and endocytosis in the garland cell of the temperature-sensitive mutant of Drosophila melanogaster, shibirets1

  1983influential reference
• Parts I and II

  1982cited by this paper
• Genetic transformation of Drosophila with transposable element vectors.

  1982cited by this paper
• Dynamin and Its Role in Membrane Fission

  year unknowncited by this paper

• Endocytosis of Wnt ligands from surrounding epithelial cells positions microtubule nucleation sites at dendrite branch points

  2025cites this paper
• Hsc70-4: An unanticipated mediator of dsRNA internalization in Drosophila

  2025cites this paper
• Dectin-1 stimulating β-glucans inhibit Chlamydia infections both in vitro and in vivo

  2025cites this paper
• A high‐throughput screen in mESCs to identify the cross‐talk between signaling, endocytosis, and pluripotency

  2024cites this paper
• Hsc70-4 mediates internalization of environmental dsRNA at the surface of Drosophila S2 cells

  2023cites this paper
• Cdc37 as a Co-chaperone to Hsp90.

  2023cites this paper
• Peripheral nerves directly mediate the transneuronal translocation of silver nanomaterials from the gut to central nervous system

  2023cites this paper
• The TGEV Membrane Protein Interacts with HSC70 To Direct Virus Internalization through Clathrin-Mediated Endocytosis

  2023cites this paper
• Elongator stabilizes microtubules to control central spindle asymmetry and polarized trafficking of cell fate determinants

  2022cites this paper
• Graphene-Mediated Antioxidant Enzyme Activity and Respiration in Plant Roots

  2022cites this paper
• Clearance of variant Creutzfeldt–Jakob disease prions in vivo by the Hsp70 disaggregase system

  2022cites this paper
• Parkinson disease-associated Leucine-rich repeat kinase regulates UNC-104-dependent axonal transport of Arl8-positive vesicles in Drosophila

  2022cites this paper
• Male-female communication enhances release of extracellular vesicles leading to high fertility in Drosophila

  2022cites this paper
• Drosophila melanogaster: a simple genetic model of kidney structure, function and disease

  2022cites this paper
• TOR signalling regulates epithelial cell shape transition in Drosophila oogenesis

  2022cites this paper
• Graphene promotes plant root growth by enhancing root respiration

  2021cites this paper
• Endocytosis mediated by an atypical CUBAM complex modulates slit diaphragm dynamics in nephrocytes

  2021cites this paper
• Post-Transcriptional Inhibition Of Hsc70-4/Hspa8 Expression Leads To Synaptic Vesicle Cycling Defects In Multiple Models Of Als

  2021cites this paper
• A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience

  2021cites this paper
• Calcium waves facilitate and coordinate the contraction of endfeet actin stress fibers in Drosophila interommatidial cells

  2021cites this paper
• De novo endocytic clathrin coats develop curvature at early stages of their formation.

  2021cites this paper
• Management of Hsp90-Dependent Protein Folding by Small Molecules Targeting the Aha1 Co-Chaperone.

  2020cites this paper
• Mechanism and Complex Roles of HSC70 in Viral Infections

  2020cites this paper
• Interplay between actomyosin and E-cadherin dynamics regulates cell shape in the Drosophila embryonic epidermis

  2020cites this paper
• Phosphorylation of human AQP2 and its role in trafficking.

  2020cites this paper
• Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises

  2020cites this paper
• Activity-dependent endocytosis of Wingless regulates synaptic plasticity in the Drosophila visual system.

  2020cites this paper
• Comprehensive analysis of lncRNA-mRNA regulatory network in BmNPV infected cells treated with Hsp90 inhibitor.

  2020cites this paper
• Dopamine Transporter is Downregulated and its Association with Chaperone Protein Hsc70 is Enhanced by Activation of Dopamine D3 Receptor.

  2020cites this paper
• HSPA8/HSC70 in Immune Disorders: A Molecular Rheostat that Adjusts Chaperone-Mediated Autophagy Substrates

  2019cites this paper
• Novel roles of ErbB3 receptor tyrosine kinase in vesicular trafficking

  2019influential citation
• A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation

  2019cites this paper
• Interplay between cortical actin and E-cadherin dynamics regulates cell shape in the Drosophila embryonic epidermis

  2019cites this paper
• Endocytic Clathrin Coats Develop Curvature at Early Stages of Their Formation

  2019cites this paper
• E-cadherin endocytosis is modulated by p120-catenin through the opposing actions of RhoA and Arf1

  2018cites this paper
• Drosophila R8 photoreceptor cell subtype specification requires Notch and hibris

  2018cites this paper
• Reconfiguration of a Multi-oscillator Network by Light in the Drosophila Circadian Clock.

  2018cites this paper
• To be or not to be... secreted as exosomes, a balance finely tuned by the mechanisms of biogenesis.

  2018cites this paper
• Management of Hsp90-Dependent Protein Folding by Small Molecule Targeting the Aha1 Co-Chaperone

  2018cites this paper
• RNA-Seq analysis of Polyrhachis vicina Roger and insights into the heat shock protein 90 and 70 families

  2018cites this paper
• Molecular Chaperone Hsp70 and Its Constitutively Active Form Hsc70 Play an Indispensable Role During Eye Development of Drosophila melanogaster

  2017cites this paper
• Dissecting the Role of the Extracellular Matrix in Heart Disease: Lessons from the Drosophila Genetic Model

  2017cites this paper
• Differential transcriptome analysis supports Rhodnius montenegrensis and Rhodnius robustus (Hemiptera, Reduviidae, Triatominae) as distinct species

  2017cites this paper
• Post-transcriptional Inhibition of Hsc70-4/HSPA8 Expression Leads to Synaptic Vesicle Cycling Defects in Multiple Models of ALS.

  2017cites this paper
• Generating genomic resources for two crustacean species and their application to the study of White Spot Disease

  2016influential citation
• Role of Auxilin and Heat Shock Protein 70kDa in Clathrin Uncoating

  2016influential citation
• Selective endosomal microautophagy is starvation-inducible in Drosophila

  2016cites this paper
• AP-2-complex-mediated endocytosis of Drosophila Crumbs regulates polarity by antagonizing Stardust

  2015cites this paper
• Endocytic pathway mediates refractoriness of insect Bactrocera dorsalis to RNA interference

  2015cites this paper
• Heat shock cognate protein 70 isoform D is required for clathrin-dependent endocytosis of Japanese encephalitis virus in C6/36 cells.

  2015cites this paper
• Hsc70 chaperone activity underlies Trio GEF function in axon growth and guidance induced by netrin-1

  2015cites this paper
• 1 AP-2 complex-mediated endocytosis of Drosophila Crumbs regulates polarity via antagonizing

  2015cites this paper
• Polarized E-cadherin endocytosis directs actomyosin remodeling during embryonic wound repair

  2015cites this paper
• Endocytosis of Fgf8 Is a Double-Stage Process and Regulates Spreading and Signaling

  2014cites this paper
• A central role for inducible heat‐shock protein 70 in autoimmune vitiligo

  2013cites this paper
• A Genome-Wide RNAi Screen for Modifiers of Polyglutamine-Induced Neurotoxicity in Drosophila

  2013cites this paper
• Drosophila EHBP1 regulates Scabrous secretion during Notch-mediated lateral inhibition

  2013cites this paper
• Disruption of Drosophila melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated with Altered Developmental Signaling

  2013cites this paper
• Numb/Numbl-Opo antagonism controls retinal epithelium morphogenesis by regulating integrin endocytosis.

  2012cites this paper
• The apoptotic engulfment protein Ced-6 participates in clathrin-mediated yolk uptake in Drosophila egg chambers

  2012cites this paper
• Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential.

  2012cites this paper
• Liquid facets-Related (lqfR) Is Required for Egg Chamber Morphogenesis during Drosophila Oogenesis

  2011cites this paper
• Imaging Single Endocytic Events Reveals Diversity in Clathrin, Dynamin and Vesicle Dynamics

  2011cites this paper
• Clathrin-mediated endocytosis of yolk protein in the Drosophila oocyte

  2011cites this paper
• Airway maturation in Drosophila

  2011cites this paper
• Nak regulates localization of clathrin sites in higher-order dendrites to promote local dendrite growth.

  2011cites this paper
• Auxilin is required for formation of Golgi-derived clathrin-coated vesicles during Drosophila spermatogenesis

  2011influential citation
• Drosophila Rolling Blackout Displays Lipase Domain‐Dependent and ‐Independent Endocytic Functions Downstream of Dynamin

  2010cites this paper
• Identifying cellular pathways modulated by Drosophila palmitoyl-protein thioesterase 1 function.

  2010cites this paper
• Regulation of endocytic recycling in Caenorhabditis elegans

  2010influential citation
• Identificação de proteínas que interagem com a porção citoplasmática C-terminal do receptor para Angiotensina II (AT1aR) em células de tecido renal

  2010cites this paper
• ESCRT & Co

  2010cites this paper
• A Genomewide RNA Interference Screen for Modifiers of Aggregates Formation by Mutant Huntingtin in Drosophila

  2010cites this paper
• Proteomic analysis reveals the role of synaptic vesicle cycling in sustaining the suprachiasmatic circadian clock.

  2009cites this paper
• Uptake of the Necrotic Serpin in Drosophila melanogaster via the Lipophorin Receptor-1

  2009cites this paper
• Regulation of endosomal clathrin and retromer‐mediated endosome to Golgi retrograde transport by the J‐domain protein RME‐8

  2009cites this paper
• Proteomic analysis reveals Hrs ubiquitin‐interacting motif‐mediated ubiquitin signaling in multiple cellular processes

  2009cites this paper
• Notch down-regulation by endocytosis is essential for pigment cell determination and survival in the Drosophila retina.

  2009cites this paper
• Perturbing Dynamin Reveals Potent Effects on the Drosophila Circadian Clock

  2009cites this paper
• Rolling blackout is required for bulk endocytosis in non-neuronal cells and neuronal synapses

  2009cites this paper
• Expression and localization of clathrin heavy chain in Drosophila melanogaster.

  2009cites this paper
• Regulation of aquaporin-2 trafficking.

  2009cites this paper
• Drosophila Past1 is involved in endocytosis and is required for germline development and survival of the adult fly

  2009cites this paper
• Flying podocytes.

  2009cites this paper
• Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis.

  2009cites this paper
• Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1, direct adhesion, fusion and formation of a slit diaphragm-like structure in insect nephrocytes

  2009cites this paper
• The clathrin-binding motif and the J-domain of Drosophila Auxilin are essential for facilitating Notch ligand endocytosis

  2008cites this paper
• Neural recognition molecule CHL1 : regulation of the activity of the trimeric protein complex Csp/Hsc70/Sgt and synaptic vesicle recycling in Mus musculus (Linnaeus, 1758)

  2008cites this paper
• Local actin-dependent endocytosis is zygotically controlled to initiate Drosophila cellularization.

  2008cites this paper
• Synaptic Vesicle Endocytosis

  2008cites this paper
• Temporal identity in axonal target layer recognition

  2008cites this paper
• Reactive oxygen species act remotely to cause synapse loss in a Drosophila model of developmental mitochondrial encephalopathy

  2008cites this paper
• Multiple Hsp70 Isoforms in the Eukaryotic Cytosol: Mere Redundancy or Functional Specificity?

  2008cites this paper
• Wurst is essential for airway clearance and respiratory-tube size control

  2007cites this paper
• Sequential pulses of apical epithelial secretion and endocytosis drive airway maturation in Drosophila.

  2007cites this paper
• Proteomic Identification of Novel Proteins in Cortical Lewy Bodies

  2007cites this paper
• Mechanisms of Chlamydia trachomatis Entry into Nonphagocytic Cells

  2007influential citation
• Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation

  2007cites this paper
• The O-fucosyltransferase O-fut1 is an extracellular component that is essential for the constitutive endocytic trafficking of Notch in Drosophila

  2007cites this paper
• Heat Shock Protein 70 Interacts with Aquaporin-2 and Regulates Its Trafficking*

  2007cites this paper