β2-adrenergic Agonists Rescue Lysosome Acidification and Function in PSEN1 Deficiency by Reversing Defective ER-to-lysosome Delivery of ClC-7.

Adrenergic beta-2 Receptor Agonists / pharmacology Alzheimer Disease / drug therapy Animals Calcium / metabolism Chloride Channels / metabolism Chlorides / metabolism Endoplasmic Reticulum / drug effects Fibroblasts / drug effects Humans Hydrogen-Ion Concentration Lysosomes / drug effects Mice Mice, Knockout Mutation Presenilin-1 / genetics Receptors, Adrenergic, beta-2 / chemistry
PKA RNA-seq acidification chloride lysosome

Journal

Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R

Informations de publication

Date de publication:
03 04 2020
Historique:
received: 16 10 2019
revised: 11 02 2020
accepted: 12 02 2020
pubmed: 28 2 2020
medline: 3 11 2020
entrez: 28 2 2020
Statut: ppublish

Résumé

Lysosomal dysfunction is considered pathogenic in Alzheimer disease (AD). Loss of presenilin-1 (PSEN1) function causing AD impedes acidification via defective vacuolar ATPase (vATPase) V0a1 subunit delivery to lysosomes. We report that isoproterenol (ISO) and related β2-adrenergic agonists reacidify lysosomes in PSEN1 Knock out (KO) cells and fibroblasts from PSEN1 familial AD patients, which restores lysosomal proteolysis, calcium homeostasis, and normal autophagy flux. We identify a novel rescue mechanism involving Portein Kinase A (PKA)-mediated facilitation of chloride channel-7 (ClC-7) delivery to lysosomes which reverses markedly lowered chloride (Cl

Identifiants

DOI: 10.1016/j.jmb.2020.02.021 PMID: 32105735 PMC: PMC7211125
pubmed: 32105735
pii: S0022-2836(20)30194-7
doi: 10.1016/j.jmb.2020.02.021
pmc: PMC7211125
mid: NIHMS1568685
pii:
doi:

Substances chimiques

Adrenergic beta-2 Receptor Agonists 0
Chloride Channels 0
Chlorides 0
Clcn7 protein, mouse 0
PSEN1 protein, human 0
Presenilin-1 0
Receptors, Adrenergic, beta-2 0
presenilin 1, mouse 0
Calcium SY7Q814VUP

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2633-2650

Subventions

Organisme : NIA NIH HHS
ID : P01 AG017617
Pays : United States

Informations de copyright

Published by Elsevier Ltd.

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Auteurs

Ju-Hyun Lee (JH)

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA; Department of Psychiatry, Langone Medical Center, New York, NY, 10016, USA. Electronic address: ju-hyun.lee@nki.rfmh.org.

Devin M Wolfe (DM)

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA.

Sandipkumar Darji (S)

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA.

Mary Kate McBrayer (MK)

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA.

Daniel J Colacurcio (DJ)

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA.

Asok Kumar (A)

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA.

Philip Stavrides (P)

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA.

Panaiyur S Mohan (PS)

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA; Department of Psychiatry, Langone Medical Center, New York, NY, 10016, USA.

Ralph A Nixon (RA)

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA; Department of Psychiatry, Langone Medical Center, New York, NY, 10016, USA; Department of Cell Biology, Langone Medical Center, New York, NY, 10016, USA; Neuroscience Institute, New York University, New York, NY 10016, USA. Electronic address: ralph.nixon@nki.rfmh.org.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Agents neuromédiateurs › Agents adrénergiques › Agonistes adrénergiques › Agonistes bêta-adrénergiques › Agonistes des récepteurs béta-2 adrénergiques › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Eucaryotes › Animaux › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Calcium › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Canaux chlorure › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Produits chimiques inorganiques › Électrolytes › Ions › Anions › Chlorures › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Réticulum endoplasmique › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Phénomènes chimiques › Concentration en ions d'hydrogène › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Vésicules cytoplasmiques › Lysosomes › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Présénilines › Préséniline-1 › β2-adrenergic Agonists Rescue Lysosome...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs catécholaminergiques › Récepteurs adrénergiques › Récepteurs bêta-adrénergiques › Récepteurs bêta-2 adrénergiques › β2-adrenergic Agonists Rescue Lysosome...