UvA-DARE (Digital The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles

ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of (ART) and SHH. Our findings show CHMP1A loss impairs secretion of SHH on ART-EVs, providing molecular mechanistic insights into the role of ESCRT proteins and EVs in the brain. gRNA a plasmid, sequence: GAAGGACTCCAAGGCGGAGC. GFP cells colonies identify homozygous frameshift mutations in CHMP1A Controls were monoclonal lines from the same experiments shown to be WT by Sanger sequencing. Primers used to genotype were Transfer stacks (Invitrogen) prior to primary antibody incubation overnight at 4 (cid:1) C. Membranes were revealed by chemiluminescence using Clarity or Clarity Max Western ECL Blotting Substrates (Bio-Rad) and images were acquired using ChemiDoc Touch system (Bio-Rad).

[1]  John A.G. Briggs,et al.  The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer , 2018, Cell.

[2]  L. Fradkin,et al.  Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons , 2018, Cell.

[3]  K. Hayworth,et al.  Enhanced FIB-SEM systems for large-volume 3D imaging , 2017, eLife.

[4]  Thomas Burger,et al.  DAPAR & ProStaR: software to perform statistical analyses in quantitative discovery proteomics , 2016, Bioinform..

[5]  A. Nimmerjahn,et al.  TAM receptors regulate multiple features of microglial physiology , 2016, Nature.

[6]  F. Wendler,et al.  Extracellular vesicles round off communication in the nervous system , 2016, Nature Reviews Neuroscience.

[7]  Brett J. Graham,et al.  Anatomy and function of an excitatory network in the visual cortex , 2016, Nature.

[8]  C. Théry,et al.  Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes , 2016, Proceedings of the National Academy of Sciences.

[9]  S. Mayor,et al.  Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion , 2015, Molecular biology of the cell.

[10]  Jennifer Luebke,et al.  Depletion of microglia and inhibition of exosome synthesis halt tau propagation , 2015, Nature Neuroscience.

[11]  James Briscoe,et al.  Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms , 2015, Nature Communications.

[12]  Maria K. Lehtinen,et al.  Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production , 2015, The Journal of Neuroscience.

[13]  G. Raposo,et al.  Vertebrate Hedgehog is secreted on two types of extracellular vesicles with different signaling properties , 2014, Scientific Reports.

[14]  F. Wendler,et al.  The ESCRT machinery regulates the secretion and long-range activity of Hedgehog , 2014, Nature.

[15]  David M Feliciano,et al.  Cerebrospinal Fluid Extracellular Vesicles Undergo Age Dependent Declines and Contain Known and Novel Non-coding RNAs , 2014, PloS one.

[16]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[17]  Chad A. Cowan,et al.  Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing. , 2014, Cell stem cell.

[18]  C. Teunissen,et al.  Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset. , 2014, Journal of proteomics.

[19]  Marco Y. Hein,et al.  Accurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ * , 2014, Molecular & Cellular Proteomics.

[20]  Christine Carapito,et al.  MSDA, a proteomics software suite for in‐depth Mass Spectrometry Data Analysis using grid computing , 2014, Proteomics.

[21]  Andrew F. Hill,et al.  Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles , 2014, Journal of extracellular vesicles.

[22]  Clotilde Théry,et al.  Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles , 2013, Journal of Cell Science.

[23]  J. D. Macklis,et al.  Molecular logic of neocortical projection neuron specification, development and diversity , 2013, Nature Reviews Neuroscience.

[24]  Nicole H. Wilson,et al.  Sonic Hedgehog Regulates Its Own Receptor on Postcrossing Commissural Axons in a Glypican1-Dependent Manner , 2013, Neuron.

[25]  Aiman S Saab,et al.  Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication , 2013, PLoS biology.

[26]  W. Sundquist,et al.  Membrane fission reactions of the mammalian ESCRT pathway. , 2013, Annual review of biochemistry.

[27]  Cole Trapnell,et al.  TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions , 2013, Genome Biology.

[28]  V. Budnik,et al.  Regulation of Postsynaptic Retrograde Signaling by Presynaptic Exosome Release , 2013, Neuron.

[29]  Athar N. Malik,et al.  CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development , 2012, Nature Genetics.

[30]  Ylva Ivarsson,et al.  Syndecan–syntenin–ALIX regulates the biogenesis of exosomes , 2012, Nature Cell Biology.

[31]  Jeremy G. Carlton,et al.  ESCRT-III Governs the Aurora B–Mediated Abscission Checkpoint Through CHMP4C , 2012, Science.

[32]  Anatol C. Kreitzer,et al.  Sonic Hedgehog Expression in Corticofugal Projection Neurons Directs Cortical Microcircuit Formation , 2012, Neuron.

[33]  J. Leszyk,et al.  Mechanism of Evenness Interrupted (Evi)-Exosome Release at Synaptic Boutons* , 2012, The Journal of Biological Chemistry.

[34]  E. Clementi,et al.  Microvesicles released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism , 2012, The EMBO journal.

[35]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[36]  C. Théry,et al.  Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation , 2012, Journal of extracellular vesicles.

[37]  S. Mackem,et al.  Analysis of mutants with altered shh activity and posterior digit loss supports a biphasic model for shh function as a morphogen and mitogen , 2011, Developmental dynamics : an official publication of the American Association of Anatomists.

[38]  Mark T. Handley,et al.  Loss-of-function mutations in RAB18 cause Warburg micro syndrome. , 2011, American journal of human genetics.

[39]  G. Lachenal,et al.  Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity , 2011, Molecular and Cellular Neuroscience.

[40]  C. Walsh,et al.  Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors , 2010, Development.

[41]  S. Dymecki,et al.  Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus. , 2010, Developmental biology.

[42]  Bulent Ataman,et al.  Trans-Synaptic Transmission of Vesicular Wnt Signals through Evi/Wntless , 2009, Cell.

[43]  R. Pepperkok,et al.  Rab18 and Rab43 have key roles in ER-Golgi trafficking , 2008, Journal of Cell Science.

[44]  A. McMahon,et al.  Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning , 2008, Development.

[45]  S. Young,et al.  ESCRT-III Dysfunction Causes Autophagosome Accumulation and Neurodegeneration , 2007, Current Biology.

[46]  M. Greenberg,et al.  Polarized Signaling Endosomes Coordinate BDNF-Induced Chemotaxis of Cerebellar Precursors , 2007, Neuron.

[47]  M. Malagón,et al.  Rab18 Inhibits Secretory Activity in Neuroendocrine Cells by Interacting with Secretory Granules , 2007, Traffic.

[48]  C. Chiang,et al.  Region-specific requirement for cholesterol modification of sonic hedgehog in patterning the telencephalon and spinal cord , 2007, Development.

[49]  G. Fishell,et al.  Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development , 2006, Nature Reviews Neuroscience.

[50]  H. Stenmark,et al.  Endosomal and non-endosomal functions of ESCRT proteins. , 2006, Trends in cell biology.

[51]  A. Joyner,et al.  The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation , 2006, Development.

[52]  C. Futter,et al.  EGF stimulates annexin 1‐dependent inward vesiculation in a multivesicular endosome subpopulation , 2006, The EMBO journal.

[53]  N. Hirokawa,et al.  FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left–right determination , 2005, Nature.

[54]  Suzanne Eaton,et al.  Lipoprotein particles are required for Hedgehog and Wingless signalling , 2005, Nature.

[55]  Paola Arlotta,et al.  Neuronal Subtype-Specific Genes that Control Corticospinal Motor Neuron Development In Vivo , 2005, Neuron.

[56]  A. Joyner,et al.  Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum development , 2004, Development.

[57]  G. Raposo,et al.  Exosomes: endosomal-derived vesicles shipping extracellular messages. , 2004, Current opinion in cell biology.

[58]  A. McMahon,et al.  The Morphogen Sonic Hedgehog Is an Axonal Chemoattractant that Collaborates with Netrin-1 in Midline Axon Guidance , 2003, Cell.

[59]  J. Slot,et al.  Immunoelectron Microscopic Localization of Cholesterol Using Biotinylated and Non-cytolytic Perfringolysin O , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[60]  G. Raposo,et al.  Intestinal epithelial cells secrete exosome-like vesicles. , 2001, Gastroenterology.

[61]  S. Hollenberg,et al.  CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins. , 2001, Journal of cell science.

[62]  Xin Zeng,et al.  A freely diffusible form of Sonic hedgehog mediates long-range signalling , 2001, Nature.

[63]  A. Ruiz i Altaba,et al.  Sonic hedgehog regulates the growth and patterning of the cerebellum. , 1999, Development.

[64]  M. Scott,et al.  Altered neural cell fates and medulloblastoma in mouse patched mutants. , 1997, Science.

[65]  J. Vandekerckhove,et al.  Tmp21 and p24A, Two Type I Proteins Enriched in Pancreatic Microsomal Membranes, Are Members of a Protein Family Involved in Vesicular Trafficking* , 1996, The Journal of Biological Chemistry.

[66]  T. Jessell,et al.  Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis , 1995, Cell.

[67]  R. Espinosa,et al.  axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase , 1991, Molecular and cellular biology.

[68]  P. S. St George-Hyslop,et al.  TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. , 2006, Nature.

[69]  Conrad C. Huang,et al.  BayGenomics: a resource of insertional mutations in mouse embryonic stem cells , 2003, Nucleic Acids Res..

[70]  M. Scott,et al.  Control of Neuronal Precursor Proliferation in the Cerebellum by Sonic Hedgehog , 1999, Neuron.