The VPS33B-binding protein VPS16B is required in megakaryocyte and platelet α-granule biogenesis.
Identifieur interne : 001113 ( Main/Exploration ); précédent : 001112; suivant : 001114The VPS33B-binding protein VPS16B is required in megakaryocyte and platelet α-granule biogenesis.
Auteurs : Denisa Urban [Canada] ; Ling Li ; Hilary Christensen ; Fred G. Pluthero ; Shao Zun Chen ; Michael Puhacz ; Parvesh M. Garg ; Kiran K. Lanka ; James J. Cummings ; Helmut Kramer ; James D. Wasmuth ; John Parkinson ; Walter H A. KahrSource :
- Blood [ 1528-0020 ] ; 2012.
English descriptors
- KwdEn :
- Arthrogryposis (metabolism), Arthrogryposis (pathology), Blood Platelets (metabolism), Blood Platelets (pathology), Carrier Proteins (analysis), Carrier Proteins (genetics), Carrier Proteins (metabolism), Cell Line, Cholestasis (metabolism), Cholestasis (pathology), Chromosomes, Human, Pair 14 (genetics), Chromosomes, Human, Pair 14 (metabolism), Codon, Nonsense, Female, Golgi Apparatus (ultrastructure), HEK293 Cells, Humans, Infant, Newborn, Megakaryocytes (metabolism), Megakaryocytes (pathology), Open Reading Frames, Phylogeny, Protein Binding, Renal Insufficiency (metabolism), Renal Insufficiency (pathology), Secretory Vesicles (metabolism), Secretory Vesicles (pathology), Vesicular Transport Proteins (metabolism).
- MESH :
- chemical , analysis : Carrier Proteins.
- chemical , genetics : Carrier Proteins.
- genetics : Chromosomes, Human, Pair 14.
- metabolism : Arthrogryposis, Blood Platelets, Carrier Proteins, Cholestasis, Chromosomes, Human, Pair 14, Megakaryocytes, Renal Insufficiency, Secretory Vesicles, Vesicular Transport Proteins.
- pathology : Arthrogryposis, Blood Platelets, Cholestasis, Megakaryocytes, Renal Insufficiency, Secretory Vesicles.
- ultrastructure : Golgi Apparatus.
- Cell Line, Codon, Nonsense, Female, HEK293 Cells, Humans, Infant, Newborn, Open Reading Frames, Phylogeny, Protein Binding.
Abstract
Patients with platelet α or dense δ-granule defects have bleeding problems. Although several proteins are known to be required for δ-granule development, less is known about α-granule biogenesis. Our previous work showed that the BEACH protein NBEAL2 and the Sec1/Munc18 protein VPS33B are required for α-granule biogenesis. Using a yeast two-hybrid screen, mass spectrometry, coimmunoprecipitation, and bioinformatics studies, we identified VPS16B as a VPS33B-binding protein. Immunoblotting confirmed VPS16B expression in various human tissues and cells including megakaryocytes and platelets, and also in megakaryocytic Dami cells. Characterization of platelets from a patient with arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome containing mutations in C14orf133 encoding VPS16B revealed pale-appearing platelets in blood films and electron microscopy revealed a complete absence of α-granules, whereas δ-granules were observed. Soluble and membrane-bound α-granule proteins were reduced or undetectable, suggesting that both releasable and membrane-bound α-granule constituents were absent. Immunofluorescence microscopy of Dami cells stably expressing GFP-VPS16B revealed that similar to VPS33B, GFP-VPS16B colocalized with markers of the trans-Golgi network, late endosomes and α-granules. We conclude that VPS16B, similar to its binding partner VPS33B, is essential for megakaryocyte and platelet α-granule biogenesis.
DOI: 10.1182/blood-2012-05-431205
PubMed: 23002115
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000999
- to stream PubMed, to step Curation: 000999
- to stream PubMed, to step Checkpoint: 000999
- to stream Ncbi, to step Merge: 001261
- to stream Ncbi, to step Curation: 001261
- to stream Ncbi, to step Checkpoint: 001261
- to stream Main, to step Merge: 001133
- to stream Main, to step Curation: 001113
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The VPS33B-binding protein VPS16B is required in megakaryocyte and platelet α-granule biogenesis.</title><author><name sortKey="Urban, Denisa" sort="Urban, Denisa" uniqKey="Urban D" first="Denisa" last="Urban">Denisa Urban</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Li, Ling" sort="Li, Ling" uniqKey="Li L" first="Ling" last="Li">Ling Li</name></author><author><name sortKey="Christensen, Hilary" sort="Christensen, Hilary" uniqKey="Christensen H" first="Hilary" last="Christensen">Hilary Christensen</name></author><author><name sortKey="Pluthero, Fred G" sort="Pluthero, Fred G" uniqKey="Pluthero F" first="Fred G" last="Pluthero">Fred G. Pluthero</name></author><author><name sortKey="Chen, Shao Zun" sort="Chen, Shao Zun" uniqKey="Chen S" first="Shao Zun" last="Chen">Shao Zun Chen</name></author><author><name sortKey="Puhacz, Michael" sort="Puhacz, Michael" uniqKey="Puhacz M" first="Michael" last="Puhacz">Michael Puhacz</name></author><author><name sortKey="Garg, Parvesh M" sort="Garg, Parvesh M" uniqKey="Garg P" first="Parvesh M" last="Garg">Parvesh M. Garg</name></author><author><name sortKey="Lanka, Kiran K" sort="Lanka, Kiran K" uniqKey="Lanka K" first="Kiran K" last="Lanka">Kiran K. Lanka</name></author><author><name sortKey="Cummings, James J" sort="Cummings, James J" uniqKey="Cummings J" first="James J" last="Cummings">James J. Cummings</name></author><author><name sortKey="Kramer, Helmut" sort="Kramer, Helmut" uniqKey="Kramer H" first="Helmut" last="Kramer">Helmut Kramer</name></author><author><name sortKey="Wasmuth, James D" sort="Wasmuth, James D" uniqKey="Wasmuth J" first="James D" last="Wasmuth">James D. Wasmuth</name></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name></author><author><name sortKey="Kahr, Walter H A" sort="Kahr, Walter H A" uniqKey="Kahr W" first="Walter H A" last="Kahr">Walter H A. Kahr</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="RBID">pubmed:23002115</idno><idno type="pmid">23002115</idno><idno type="doi">10.1182/blood-2012-05-431205</idno><idno type="wicri:Area/PubMed/Corpus">000999</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000999</idno><idno type="wicri:Area/PubMed/Curation">000999</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000999</idno><idno type="wicri:Area/PubMed/Checkpoint">000999</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000999</idno><idno type="wicri:Area/Ncbi/Merge">001261</idno><idno type="wicri:Area/Ncbi/Curation">001261</idno><idno type="wicri:Area/Ncbi/Checkpoint">001261</idno><idno type="wicri:Area/Main/Merge">001133</idno><idno type="wicri:Area/Main/Curation">001113</idno><idno type="wicri:Area/Main/Exploration">001113</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The VPS33B-binding protein VPS16B is required in megakaryocyte and platelet α-granule biogenesis.</title><author><name sortKey="Urban, Denisa" sort="Urban, Denisa" uniqKey="Urban D" first="Denisa" last="Urban">Denisa Urban</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Li, Ling" sort="Li, Ling" uniqKey="Li L" first="Ling" last="Li">Ling Li</name></author><author><name sortKey="Christensen, Hilary" sort="Christensen, Hilary" uniqKey="Christensen H" first="Hilary" last="Christensen">Hilary Christensen</name></author><author><name sortKey="Pluthero, Fred G" sort="Pluthero, Fred G" uniqKey="Pluthero F" first="Fred G" last="Pluthero">Fred G. Pluthero</name></author><author><name sortKey="Chen, Shao Zun" sort="Chen, Shao Zun" uniqKey="Chen S" first="Shao Zun" last="Chen">Shao Zun Chen</name></author><author><name sortKey="Puhacz, Michael" sort="Puhacz, Michael" uniqKey="Puhacz M" first="Michael" last="Puhacz">Michael Puhacz</name></author><author><name sortKey="Garg, Parvesh M" sort="Garg, Parvesh M" uniqKey="Garg P" first="Parvesh M" last="Garg">Parvesh M. Garg</name></author><author><name sortKey="Lanka, Kiran K" sort="Lanka, Kiran K" uniqKey="Lanka K" first="Kiran K" last="Lanka">Kiran K. Lanka</name></author><author><name sortKey="Cummings, James J" sort="Cummings, James J" uniqKey="Cummings J" first="James J" last="Cummings">James J. Cummings</name></author><author><name sortKey="Kramer, Helmut" sort="Kramer, Helmut" uniqKey="Kramer H" first="Helmut" last="Kramer">Helmut Kramer</name></author><author><name sortKey="Wasmuth, James D" sort="Wasmuth, James D" uniqKey="Wasmuth J" first="James D" last="Wasmuth">James D. Wasmuth</name></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name></author><author><name sortKey="Kahr, Walter H A" sort="Kahr, Walter H A" uniqKey="Kahr W" first="Walter H A" last="Kahr">Walter H A. Kahr</name></author></analytic><series><title level="j">Blood</title><idno type="eISSN">1528-0020</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Arthrogryposis (metabolism)</term><term>Arthrogryposis (pathology)</term><term>Blood Platelets (metabolism)</term><term>Blood Platelets (pathology)</term><term>Carrier Proteins (analysis)</term><term>Carrier Proteins (genetics)</term><term>Carrier Proteins (metabolism)</term><term>Cell Line</term><term>Cholestasis (metabolism)</term><term>Cholestasis (pathology)</term><term>Chromosomes, Human, Pair 14 (genetics)</term><term>Chromosomes, Human, Pair 14 (metabolism)</term><term>Codon, Nonsense</term><term>Female</term><term>Golgi Apparatus (ultrastructure)</term><term>HEK293 Cells</term><term>Humans</term><term>Infant, Newborn</term><term>Megakaryocytes (metabolism)</term><term>Megakaryocytes (pathology)</term><term>Open Reading Frames</term><term>Phylogeny</term><term>Protein Binding</term><term>Renal Insufficiency (metabolism)</term><term>Renal Insufficiency (pathology)</term><term>Secretory Vesicles (metabolism)</term><term>Secretory Vesicles (pathology)</term><term>Vesicular Transport Proteins (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Carrier Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Carrier Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Chromosomes, Human, Pair 14</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Arthrogryposis</term><term>Blood Platelets</term><term>Carrier Proteins</term><term>Cholestasis</term><term>Chromosomes, Human, Pair 14</term><term>Megakaryocytes</term><term>Renal Insufficiency</term><term>Secretory Vesicles</term><term>Vesicular Transport Proteins</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Arthrogryposis</term><term>Blood Platelets</term><term>Cholestasis</term><term>Megakaryocytes</term><term>Renal Insufficiency</term><term>Secretory Vesicles</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Golgi Apparatus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Codon, Nonsense</term><term>Female</term><term>HEK293 Cells</term><term>Humans</term><term>Infant, Newborn</term><term>Open Reading Frames</term><term>Phylogeny</term><term>Protein Binding</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Patients with platelet α or dense δ-granule defects have bleeding problems. Although several proteins are known to be required for δ-granule development, less is known about α-granule biogenesis. Our previous work showed that the BEACH protein NBEAL2 and the Sec1/Munc18 protein VPS33B are required for α-granule biogenesis. Using a yeast two-hybrid screen, mass spectrometry, coimmunoprecipitation, and bioinformatics studies, we identified VPS16B as a VPS33B-binding protein. Immunoblotting confirmed VPS16B expression in various human tissues and cells including megakaryocytes and platelets, and also in megakaryocytic Dami cells. Characterization of platelets from a patient with arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome containing mutations in C14orf133 encoding VPS16B revealed pale-appearing platelets in blood films and electron microscopy revealed a complete absence of α-granules, whereas δ-granules were observed. Soluble and membrane-bound α-granule proteins were reduced or undetectable, suggesting that both releasable and membrane-bound α-granule constituents were absent. Immunofluorescence microscopy of Dami cells stably expressing GFP-VPS16B revealed that similar to VPS33B, GFP-VPS16B colocalized with markers of the trans-Golgi network, late endosomes and α-granules. We conclude that VPS16B, similar to its binding partner VPS33B, is essential for megakaryocyte and platelet α-granule biogenesis.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><noCountry><name sortKey="Chen, Shao Zun" sort="Chen, Shao Zun" uniqKey="Chen S" first="Shao Zun" last="Chen">Shao Zun Chen</name><name sortKey="Christensen, Hilary" sort="Christensen, Hilary" uniqKey="Christensen H" first="Hilary" last="Christensen">Hilary Christensen</name><name sortKey="Cummings, James J" sort="Cummings, James J" uniqKey="Cummings J" first="James J" last="Cummings">James J. Cummings</name><name sortKey="Garg, Parvesh M" sort="Garg, Parvesh M" uniqKey="Garg P" first="Parvesh M" last="Garg">Parvesh M. Garg</name><name sortKey="Kahr, Walter H A" sort="Kahr, Walter H A" uniqKey="Kahr W" first="Walter H A" last="Kahr">Walter H A. Kahr</name><name sortKey="Kramer, Helmut" sort="Kramer, Helmut" uniqKey="Kramer H" first="Helmut" last="Kramer">Helmut Kramer</name><name sortKey="Lanka, Kiran K" sort="Lanka, Kiran K" uniqKey="Lanka K" first="Kiran K" last="Lanka">Kiran K. Lanka</name><name sortKey="Li, Ling" sort="Li, Ling" uniqKey="Li L" first="Ling" last="Li">Ling Li</name><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><name sortKey="Pluthero, Fred G" sort="Pluthero, Fred G" uniqKey="Pluthero F" first="Fred G" last="Pluthero">Fred G. Pluthero</name><name sortKey="Puhacz, Michael" sort="Puhacz, Michael" uniqKey="Puhacz M" first="Michael" last="Puhacz">Michael Puhacz</name><name sortKey="Wasmuth, James D" sort="Wasmuth, James D" uniqKey="Wasmuth J" first="James D" last="Wasmuth">James D. Wasmuth</name></noCountry><country name="Canada"><region name="Ontario"><name sortKey="Urban, Denisa" sort="Urban, Denisa" uniqKey="Urban D" first="Denisa" last="Urban">Denisa Urban</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001113 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001113 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:23002115
|texte= The VPS33B-binding protein VPS16B is required in megakaryocyte and platelet α-granule biogenesis.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:23002115" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |