Chorea-related mutations in PDE10A result in aberrant compartmentalization and functionality of the enzyme
A robust body of evidence supports the concept that phosphodiesterase 10A (PDE10A) activity in the basal ganglia orchestrates the control of coordinated movement in human subjects. Although human mutations in the PDE10A gene manifest in hyperkinetic movement disorders that phenocopy many features of...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 1; pp. 677 - 688 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
07.01.2020
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Subjects | |
Online Access | Get full text |
ISSN | 0027-8424 1091-6490 1091-6490 |
DOI | 10.1073/pnas.1916398117 |
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Abstract | A robust body of evidence supports the concept that phosphodiesterase 10A (PDE10A) activity in the basal ganglia orchestrates the control of coordinated movement in human subjects. Although human mutations in the PDE10A gene manifest in hyperkinetic movement disorders that phenocopy many features of early Huntington’s disease, characterization of the maladapted molecular mechanisms and aberrant signaling processes that underpin these conditions remains scarce. Recessive mutations in the GAF-A domain have been shown to impair PDE10A function due to the loss of striatal PDE10A protein levels, but here we show that this paucity is caused by irregular intracellular trafficking and increased PDE10A degradation in the cytosolic compartment. In contrast to GAF-A mutants, dominant mutations in the GAF-B domain of PDE10A induce PDE10A misfolding, a common pathological phenotype in many neurodegenerative diseases. These data demonstrate that the function of striatal PDE10A is compromised in disorders where disease-associated mutations trigger a reduction in the fidelity of PDE compartmentalization. |
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AbstractList | A robust body of evidence supports the concept that phosphodiesterase 10A (PDE10A) activity in the basal ganglia orchestrates the control of coordinated movement in human subjects. Although human mutations in the PDE10A gene manifest in hyperkinetic movement disorders that phenocopy many features of early Huntington's disease, characterization of the maladapted molecular mechanisms and aberrant signaling processes that underpin these conditions remains scarce. Recessive mutations in the GAF-A domain have been shown to impair PDE10A function due to the loss of striatal PDE10A protein levels, but here we show that this paucity is caused by irregular intracellular trafficking and increased PDE10A degradation in the cytosolic compartment. In contrast to GAF-A mutants, dominant mutations in the GAF-B domain of PDE10A induce PDE10A misfolding, a common pathological phenotype in many neurodegenerative diseases. These data demonstrate that the function of striatal PDE10A is compromised in disorders where disease-associated mutations trigger a reduction in the fidelity of PDE compartmentalization.A robust body of evidence supports the concept that phosphodiesterase 10A (PDE10A) activity in the basal ganglia orchestrates the control of coordinated movement in human subjects. Although human mutations in the PDE10A gene manifest in hyperkinetic movement disorders that phenocopy many features of early Huntington's disease, characterization of the maladapted molecular mechanisms and aberrant signaling processes that underpin these conditions remains scarce. Recessive mutations in the GAF-A domain have been shown to impair PDE10A function due to the loss of striatal PDE10A protein levels, but here we show that this paucity is caused by irregular intracellular trafficking and increased PDE10A degradation in the cytosolic compartment. In contrast to GAF-A mutants, dominant mutations in the GAF-B domain of PDE10A induce PDE10A misfolding, a common pathological phenotype in many neurodegenerative diseases. These data demonstrate that the function of striatal PDE10A is compromised in disorders where disease-associated mutations trigger a reduction in the fidelity of PDE compartmentalization. Phosphodiesterase 10A (PDE10A) is as a target of interest in Huntington’s disease (HD) as levels of the enzyme have been shown to decrease prior to the development of the hallmark motor symptoms. Clearly, a better understanding of how PDE10A protein levels change as HD develops is required. Here we show that mutations in the regulatory GAF domains of PDE10A that cause hyperkinetic syndromes in humans lead to misprocessing of the PDE10A enzyme that ultimately leads to targeted degradation by the ubiquitin proteasome system or clearance by autophagy. Both mechanisms result in a paucity of PDE10A activity that lead to a loss of movement coordination. Our research suggests that similar mechanisms may underpin PDE10A loss during HD. A robust body of evidence supports the concept that phosphodiesterase 10A (PDE10A) activity in the basal ganglia orchestrates the control of coordinated movement in human subjects. Although human mutations in the PDE10A gene manifest in hyperkinetic movement disorders that phenocopy many features of early Huntington’s disease, characterization of the maladapted molecular mechanisms and aberrant signaling processes that underpin these conditions remains scarce. Recessive mutations in the GAF-A domain have been shown to impair PDE10A function due to the loss of striatal PDE10A protein levels, but here we show that this paucity is caused by irregular intracellular trafficking and increased PDE10A degradation in the cytosolic compartment. In contrast to GAF-A mutants, dominant mutations in the GAF-B domain of PDE10A induce PDE10A misfolding, a common pathological phenotype in many neurodegenerative diseases. These data demonstrate that the function of striatal PDE10A is compromised in disorders where disease-associated mutations trigger a reduction in the fidelity of PDE compartmentalization. A robust body of evidence supports the concept that phosphodiesterase 10A (PDE10A) activity in the basal ganglia orchestrates the control of coordinated movement in human subjects. Although human mutations in the PDE10A gene manifest in hyperkinetic movement disorders that phenocopy many features of early Huntington's disease, characterization of the maladapted molecular mechanisms and aberrant signaling processes that underpin these conditions remains scarce. Recessive mutations in the GAF-A domain have been shown to impair PDE10A function due to the loss of striatal PDE10A protein levels, but here we show that this paucity is caused by irregular intracellular trafficking and increased PDE10A degradation in the cytosolic compartment. In contrast to GAF-A mutants, dominant mutations in the GAF-B domain of PDE10A induce PDE10A misfolding, a common pathological phenotype in many neurodegenerative diseases. These data demonstrate that the function of striatal PDE10A is compromised in disorders where disease-associated mutations trigger a reduction in the fidelity of PDE compartmentalization. |
Author | Brandon, Nicholas J. Whiteley, Ellanor L. Sheridan, Eamonn Baillie, George S. Tejeda, Gonzalo S. Deeb, Tarek Z. Bürli, Roland W. Moss, Stephen J. |
Author_xml | – sequence: 1 givenname: Gonzalo S. surname: Tejeda fullname: Tejeda, Gonzalo S. – sequence: 2 givenname: Ellanor L. surname: Whiteley fullname: Whiteley, Ellanor L. – sequence: 3 givenname: Tarek Z. surname: Deeb fullname: Deeb, Tarek Z. – sequence: 4 givenname: Roland W. surname: Bürli fullname: Bürli, Roland W. – sequence: 5 givenname: Stephen J. surname: Moss fullname: Moss, Stephen J. – sequence: 6 givenname: Eamonn surname: Sheridan fullname: Sheridan, Eamonn – sequence: 7 givenname: Nicholas J. surname: Brandon fullname: Brandon, Nicholas J. – sequence: 8 givenname: George S. surname: Baillie fullname: Baillie, George S. |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31871190$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1002_dneu_22924 crossref_primary_10_1016_j_tig_2021_03_002 crossref_primary_10_1007_s12035_021_02621_5 crossref_primary_10_1055_a_2281_1822 crossref_primary_10_3390_cancers13153780 crossref_primary_10_1016_j_spen_2023_101088 crossref_primary_10_1093_braincomms_fcae225 crossref_primary_10_1016_j_pharmr_2025_100042 crossref_primary_10_1097_ALN_0000000000005287 crossref_primary_10_3390_ani10112013 crossref_primary_10_1002_mds_28686 crossref_primary_10_1080_14737175_2021_1840978 |
Cites_doi | 10.1016/j.jns.2016.07.033 10.1523/JNEUROSCI.22-16-07027.2002 10.1091/mbc.12.5.1393 10.1074/jbc.M308471200 10.1073/pnas.221381398 10.1083/jcb.146.6.1239 10.1001/jamaneurol.2014.1954 10.2174/092986708783330692 10.1007/978-3-319-58811-7_2 10.1016/S0092-8674(03)00939-5 10.1212/WNL.0000000000000037 10.1038/srep38681 10.1002/cne.20819 10.1523/JNEUROSCI.1635-10.2010 10.1212/WNL.0000000000002391 10.1016/j.parkreldis.2019.02.007 10.18632/oncotarget.6705 10.15252/embj.201593594 10.1002/mds.27523 10.1093/brain/awv214 10.1038/bjc.2014.22 10.1038/nm1066 10.1016/S0092-8674(00)81782-1 10.1007/s00213-006-0510-4 10.1016/j.molcel.2009.01.020 10.1038/nrneurol.2015.148 10.1038/srep27733 10.1074/jbc.C400302200 10.1038/nchem.2122 10.1074/jbc.M800595200 10.1074/jbc.M111.306183 10.1016/j.ajhg.2016.02.015 10.1111/j.1471-4159.2010.06672.x 10.1016/j.neurobiolaging.2014.06.010 10.1038/nature02264 10.1111/j.1742-4658.2009.06926.x 10.1074/jbc.M114.595769 10.3233/JHD-160195 10.1074/jbc.TM117.000117 10.1083/jcb.143.7.1883 10.1083/jcb.200810098 10.1085/jgp.118.1.63 10.1016/j.arr.2014.07.002 10.1016/S0378-1119(99)00171-7 10.1002/dneu.22534 10.1093/brain/awv219 10.1002/pro.2814 10.1038/nature02998 10.1074/jbc.M115.657668 10.1152/ajpcell.00121.2006 10.1016/j.exger.2014.09.003 10.1128/MCB.01434-12 10.1074/jbc.M112.354647 10.1083/jcb.200507002 10.1038/nrm3741 10.1016/j.pep.2014.03.010 10.1016/j.neuroscience.2003.11.009 10.1038/s41419-018-1004-0 10.1042/bj1870381 10.1002/mds.27175 10.1073/pnas.1006551107 10.3233/JHD-160211 10.1016/j.cellsig.2019.04.001 10.1111/j.1460-9568.2004.03796.x 10.1002/ajmg.a.38507 10.1016/j.ajhg.2016.03.015 10.1186/1750-1326-7-56 10.1034/j.1600-0854.2002.30602.x 10.1074/jbc.M310994200 |
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Keywords | cyclic AMP Huntington’s disease PDE10A GAF domain phosphodieaterase |
Language | English |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Edited by Joseph A. Beavo, University of Washington School of Medicine, Seattle, WA, and approved November 20, 2019 (received for review October 15, 2019) 1Present address: Department of Neurology, University of California, San Francisco, CA, 94158. 2Present address: Jnana Therapeutics, Boston, MA 02210. Author contributions: G.S.T., E.S., N.J.B., and G.S.B. conceived the study; G.S.T., E.L.W., T.Z.D., R.W.B., S.J.M., E.S., N.J.B., and G.S.B. designed research; G.S.T., E.L.W., T.Z.D., and R.W.B. performed experiments and analyzed data; G.S.T., N.J.B., and G.S.B. wrote the paper with input from all authors. |
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References | e_1_3_3_50_2 e_1_3_3_16_2 e_1_3_3_18_2 e_1_3_3_39_2 e_1_3_3_12_2 e_1_3_3_37_2 e_1_3_3_58_2 e_1_3_3_14_2 e_1_3_3_35_2 e_1_3_3_56_2 e_1_3_3_33_2 e_1_3_3_54_2 e_1_3_3_10_2 e_1_3_3_31_2 e_1_3_3_52_2 e_1_3_3_40_2 e_1_3_3_61_2 e_1_3_3_5_2 e_1_3_3_7_2 e_1_3_3_9_2 e_1_3_3_27_2 e_1_3_3_29_2 e_1_3_3_23_2 e_1_3_3_48_2 e_1_3_3_69_2 e_1_3_3_25_2 e_1_3_3_46_2 e_1_3_3_67_2 e_1_3_3_1_2 e_1_3_3_44_2 e_1_3_3_65_2 e_1_3_3_3_2 e_1_3_3_21_2 e_1_3_3_42_2 e_1_3_3_63_2 e_1_3_3_51_2 Han I. (e_1_3_3_2_2) 2010; 113 e_1_3_3_17_2 e_1_3_3_19_2 e_1_3_3_38_2 e_1_3_3_13_2 e_1_3_3_36_2 e_1_3_3_59_2 e_1_3_3_15_2 e_1_3_3_34_2 e_1_3_3_57_2 e_1_3_3_32_2 e_1_3_3_55_2 e_1_3_3_11_2 e_1_3_3_30_2 e_1_3_3_53_2 e_1_3_3_62_2 e_1_3_3_60_2 e_1_3_3_6_2 e_1_3_3_8_2 e_1_3_3_28_2 e_1_3_3_49_2 e_1_3_3_24_2 e_1_3_3_47_2 e_1_3_3_26_2 e_1_3_3_45_2 e_1_3_3_68_2 e_1_3_3_20_2 e_1_3_3_43_2 e_1_3_3_66_2 e_1_3_3_4_2 e_1_3_3_22_2 e_1_3_3_41_2 e_1_3_3_64_2 |
References_xml | – ident: e_1_3_3_5_2 doi: 10.1016/j.jns.2016.07.033 – ident: e_1_3_3_34_2 doi: 10.1523/JNEUROSCI.22-16-07027.2002 – ident: e_1_3_3_39_2 doi: 10.1091/mbc.12.5.1393 – ident: e_1_3_3_21_2 doi: 10.1074/jbc.M308471200 – ident: e_1_3_3_26_2 doi: 10.1073/pnas.221381398 – ident: e_1_3_3_61_2 doi: 10.1083/jcb.146.6.1239 – ident: e_1_3_3_12_2 doi: 10.1001/jamaneurol.2014.1954 – ident: e_1_3_3_36_2 doi: 10.2174/092986708783330692 – ident: e_1_3_3_47_2 doi: 10.1007/978-3-319-58811-7_2 – ident: e_1_3_3_38_2 doi: 10.1016/S0092-8674(03)00939-5 – ident: e_1_3_3_4_2 doi: 10.1212/WNL.0000000000000037 – ident: e_1_3_3_62_2 doi: 10.1038/srep38681 – ident: e_1_3_3_68_2 doi: 10.1002/cne.20819 – ident: e_1_3_3_19_2 doi: 10.1523/JNEUROSCI.1635-10.2010 – ident: e_1_3_3_8_2 doi: 10.1212/WNL.0000000000002391 – ident: e_1_3_3_57_2 doi: 10.1016/j.parkreldis.2019.02.007 – ident: e_1_3_3_41_2 doi: 10.18632/oncotarget.6705 – ident: e_1_3_3_55_2 doi: 10.15252/embj.201593594 – ident: e_1_3_3_17_2 doi: 10.1002/mds.27523 – ident: e_1_3_3_7_2 doi: 10.1093/brain/awv214 – ident: e_1_3_3_53_2 doi: 10.1038/bjc.2014.22 – ident: e_1_3_3_67_2 doi: 10.1038/nm1066 – ident: e_1_3_3_65_2 doi: 10.1016/S0092-8674(00)81782-1 – ident: e_1_3_3_1_2 doi: 10.1007/s00213-006-0510-4 – ident: e_1_3_3_63_2 doi: 10.1016/j.molcel.2009.01.020 – ident: e_1_3_3_11_2 doi: 10.1038/nrneurol.2015.148 – ident: e_1_3_3_44_2 doi: 10.1038/srep27733 – ident: e_1_3_3_28_2 doi: 10.1074/jbc.C400302200 – ident: e_1_3_3_60_2 doi: 10.1038/nchem.2122 – ident: e_1_3_3_49_2 doi: 10.1074/jbc.M800595200 – ident: e_1_3_3_30_2 doi: 10.1074/jbc.M111.306183 – ident: e_1_3_3_15_2 doi: 10.1016/j.ajhg.2016.02.015 – volume: 113 start-page: 1073 year: 2010 ident: e_1_3_3_2_2 article-title: Differential vulnerability of neurons in Huntington’s disease: The role of cell type-specific features publication-title: J. Neurochem. doi: 10.1111/j.1471-4159.2010.06672.x – ident: e_1_3_3_10_2 doi: 10.1016/j.neurobiolaging.2014.06.010 – ident: e_1_3_3_42_2 doi: 10.1038/nature02264 – ident: e_1_3_3_52_2 doi: 10.1111/j.1742-4658.2009.06926.x – ident: e_1_3_3_18_2 doi: 10.1074/jbc.M114.595769 – ident: e_1_3_3_22_2 doi: 10.3233/JHD-160195 – ident: e_1_3_3_32_2 doi: 10.1074/jbc.TM117.000117 – ident: e_1_3_3_37_2 doi: 10.1083/jcb.143.7.1883 – ident: e_1_3_3_35_2 doi: 10.1083/jcb.200810098 – ident: e_1_3_3_25_2 doi: 10.1085/jgp.118.1.63 – ident: e_1_3_3_31_2 doi: 10.1016/j.arr.2014.07.002 – ident: e_1_3_3_20_2 doi: 10.1016/S0378-1119(99)00171-7 – ident: e_1_3_3_29_2 doi: 10.1002/dneu.22534 – ident: e_1_3_3_6_2 doi: 10.1093/brain/awv219 – ident: e_1_3_3_59_2 doi: 10.1002/pro.2814 – ident: e_1_3_3_64_2 doi: 10.1038/nature02998 – ident: e_1_3_3_51_2 doi: 10.1074/jbc.M115.657668 – ident: e_1_3_3_27_2 doi: 10.1152/ajpcell.00121.2006 – ident: e_1_3_3_43_2 doi: 10.1016/j.exger.2014.09.003 – ident: e_1_3_3_56_2 doi: 10.1128/MCB.01434-12 – ident: e_1_3_3_50_2 doi: 10.1074/jbc.M112.354647 – ident: e_1_3_3_33_2 doi: 10.1083/jcb.200507002 – ident: e_1_3_3_54_2 doi: 10.1038/nrm3741 – ident: e_1_3_3_58_2 doi: 10.1016/j.pep.2014.03.010 – ident: e_1_3_3_9_2 doi: 10.1016/j.neuroscience.2003.11.009 – ident: e_1_3_3_45_2 doi: 10.1038/s41419-018-1004-0 – ident: e_1_3_3_69_2 doi: 10.1042/bj1870381 – ident: e_1_3_3_14_2 doi: 10.1002/mds.27175 – ident: e_1_3_3_24_2 doi: 10.1073/pnas.1006551107 – ident: e_1_3_3_23_2 doi: 10.3233/JHD-160211 – ident: e_1_3_3_48_2 doi: 10.1016/j.cellsig.2019.04.001 – ident: e_1_3_3_3_2 doi: 10.1111/j.1460-9568.2004.03796.x – ident: e_1_3_3_16_2 doi: 10.1002/ajmg.a.38507 – ident: e_1_3_3_13_2 doi: 10.1016/j.ajhg.2016.03.015 – ident: e_1_3_3_40_2 doi: 10.1186/1750-1326-7-56 – ident: e_1_3_3_46_2 doi: 10.1034/j.1600-0854.2002.30602.x – ident: e_1_3_3_66_2 doi: 10.1074/jbc.M310994200 |
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Snippet | A robust body of evidence supports the concept that phosphodiesterase 10A (PDE10A) activity in the basal ganglia orchestrates the control of coordinated... Phosphodiesterase 10A (PDE10A) is as a target of interest in Huntington’s disease (HD) as levels of the enzyme have been shown to decrease prior to the... |
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SubjectTerms | Animals Autophagy - genetics Basal ganglia Biological Sciences Cell Membrane - metabolism Chorea Corpus Striatum - cytology Corpus Striatum - pathology Cyclic AMP - metabolism Disorders Embryo, Mammalian Ganglia HEK293 Cells Human motion Humans Huntington Disease - genetics Huntington Disease - pathology Huntington's disease Huntingtons disease Hydrolysis Isoenzymes - genetics Isoenzymes - metabolism Molecular modelling Movement disorders Mutation Neostriatum Neurodegenerative diseases Neurons - cytology Neurons - enzymology Patch-Clamp Techniques Phenotypes Phosphodiesterase Phosphoric Diester Hydrolases - genetics Phosphoric Diester Hydrolases - metabolism Primary Cell Culture Protein Domains - genetics Proteolysis Rats Recombinant Proteins - genetics Recombinant Proteins - metabolism |
Title | Chorea-related mutations in PDE10A result in aberrant compartmentalization and functionality of the enzyme |
URI | https://www.jstor.org/stable/26897509 https://www.ncbi.nlm.nih.gov/pubmed/31871190 https://www.proquest.com/docview/2335154873 https://www.proquest.com/docview/2330327393 https://pubmed.ncbi.nlm.nih.gov/PMC6955301 |
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