Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation
Summary: BIN1, a member of the BAR adaptor protein family, is a significant late-onset Alzheimer disease risk factor. Here, we investigate BIN1 function in the brain using conditional knockout (cKO) models. Loss of neuronal Bin1 expression results in the select impairment of spatial learning and mem...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-03-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472030187X |
| id |
doaj-3ee20aa26dbb4398a318c588047a8aa8 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Pierre De Rossi Toshihiro Nomura Robert J. Andrew Nicolas Y. Masse Vandana Sampathkumar Timothy F. Musial Ari Sudwarts Aleksandra J. Recupero Thomas Le Metayer Mitchell T. Hansen Ha-Na Shim Sofia V. Krause David J. Freedman Vytas P. Bindokas Narayanan Kasthuri Daniel A. Nicholson Anis Contractor Gopal Thinakaran |
| spellingShingle |
Pierre De Rossi Toshihiro Nomura Robert J. Andrew Nicolas Y. Masse Vandana Sampathkumar Timothy F. Musial Ari Sudwarts Aleksandra J. Recupero Thomas Le Metayer Mitchell T. Hansen Ha-Na Shim Sofia V. Krause David J. Freedman Vytas P. Bindokas Narayanan Kasthuri Daniel A. Nicholson Anis Contractor Gopal Thinakaran Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation Cell Reports |
| author_facet |
Pierre De Rossi Toshihiro Nomura Robert J. Andrew Nicolas Y. Masse Vandana Sampathkumar Timothy F. Musial Ari Sudwarts Aleksandra J. Recupero Thomas Le Metayer Mitchell T. Hansen Ha-Na Shim Sofia V. Krause David J. Freedman Vytas P. Bindokas Narayanan Kasthuri Daniel A. Nicholson Anis Contractor Gopal Thinakaran |
| author_sort |
Pierre De Rossi |
| title |
Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation |
| title_short |
Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation |
| title_full |
Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation |
| title_fullStr |
Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation |
| title_full_unstemmed |
Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation |
| title_sort |
neuronal bin1 regulates presynaptic neurotransmitter release and memory consolidation |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2020-03-01 |
| description |
Summary: BIN1, a member of the BAR adaptor protein family, is a significant late-onset Alzheimer disease risk factor. Here, we investigate BIN1 function in the brain using conditional knockout (cKO) models. Loss of neuronal Bin1 expression results in the select impairment of spatial learning and memory. Examination of hippocampal CA1 excitatory synapses reveals a deficit in presynaptic release probability and slower depletion of neurotransmitters during repetitive stimulation, suggesting altered vesicle dynamics in Bin1 cKO mice. Super-resolution and immunoelectron microscopy localizes BIN1 to presynaptic sites in excitatory synapses. Bin1 cKO significantly reduces synapse density and alters presynaptic active zone protein cluster formation. Finally, 3D electron microscopy reconstruction analysis uncovers a significant increase in docked and reserve pools of synaptic vesicles at hippocampal synapses in Bin1 cKO mice. Our results demonstrate a non-redundant role for BIN1 in presynaptic regulation, thus providing significant insights into the fundamental function of BIN1 in synaptic physiology relevant to Alzheimer disease. : BIN1 is a significant risk factor for late-onset Alzheimer disease. BIN1 has a general role in endocytosis and membrane dynamics in non-neuronal cells. De Rossi et al. show that BIN1 localizes to presynaptic terminals and plays an indispensable role in excitatory synaptic transmission by regulating neurotransmitter vesicle dynamics. Keywords: late-onset Alzheimer disease, BIN1, Morris water maze, synaptic physiology, release probability, super-resolution, dSTORM, STED, 3D EM reconstruction, Amphiphysin 2 |
| url |
http://www.sciencedirect.com/science/article/pii/S221112472030187X |
| work_keys_str_mv |
AT pierrederossi neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT toshihironomura neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT robertjandrew neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT nicolasymasse neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT vandanasampathkumar neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT timothyfmusial neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT arisudwarts neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT aleksandrajrecupero neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT thomaslemetayer neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT mitchellthansen neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT hanashim neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT sofiavkrause neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT davidjfreedman neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT vytaspbindokas neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT narayanankasthuri neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT danielanicholson neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT aniscontractor neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation AT gopalthinakaran neuronalbin1regulatespresynapticneurotransmitterreleaseandmemoryconsolidation |
| _version_ |
1725044374501326848 |
| spelling |
doaj-3ee20aa26dbb4398a318c588047a8aa82020-11-25T01:40:39ZengElsevierCell Reports2211-12472020-03-01301035203535.e7Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory ConsolidationPierre De Rossi0Toshihiro Nomura1Robert J. Andrew2Nicolas Y. Masse3Vandana Sampathkumar4Timothy F. Musial5Ari Sudwarts6Aleksandra J. Recupero7Thomas Le Metayer8Mitchell T. Hansen9Ha-Na Shim10Sofia V. Krause11David J. Freedman12Vytas P. Bindokas13Narayanan Kasthuri14Daniel A. Nicholson15Anis Contractor16Gopal Thinakaran17Department of Neurobiology, The University of Chicago, Chicago, IL 60637, USADepartment of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USADepartment of Neurological sciences, Rush University, Chicago, IL 60612, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USA; Department of Molecular Medicine and Byrd Alzheimer’s Institute, University of South Florida, Tampa, FL 33613, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USA; Department of Molecular Medicine and Byrd Alzheimer’s Institute, University of South Florida, Tampa, FL 33613, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USAIntegrated Light Microscopy Facility, The University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USADepartment of Neurological sciences, Rush University, Chicago, IL 60612, USADepartment of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Chicago, IL, USADepartment of Neurobiology, The University of Chicago, Chicago, IL 60637, USA; Department of Neurology, The University of Chicago, Chicago, IL 60637, USA; Department of Pathology, The University of Chicago, Chicago, IL 60637, USA; Department of Molecular Medicine and Byrd Alzheimer’s Institute, University of South Florida, Tampa, FL 33613, USA; Corresponding authorSummary: BIN1, a member of the BAR adaptor protein family, is a significant late-onset Alzheimer disease risk factor. Here, we investigate BIN1 function in the brain using conditional knockout (cKO) models. Loss of neuronal Bin1 expression results in the select impairment of spatial learning and memory. Examination of hippocampal CA1 excitatory synapses reveals a deficit in presynaptic release probability and slower depletion of neurotransmitters during repetitive stimulation, suggesting altered vesicle dynamics in Bin1 cKO mice. Super-resolution and immunoelectron microscopy localizes BIN1 to presynaptic sites in excitatory synapses. Bin1 cKO significantly reduces synapse density and alters presynaptic active zone protein cluster formation. Finally, 3D electron microscopy reconstruction analysis uncovers a significant increase in docked and reserve pools of synaptic vesicles at hippocampal synapses in Bin1 cKO mice. Our results demonstrate a non-redundant role for BIN1 in presynaptic regulation, thus providing significant insights into the fundamental function of BIN1 in synaptic physiology relevant to Alzheimer disease. : BIN1 is a significant risk factor for late-onset Alzheimer disease. BIN1 has a general role in endocytosis and membrane dynamics in non-neuronal cells. De Rossi et al. show that BIN1 localizes to presynaptic terminals and plays an indispensable role in excitatory synaptic transmission by regulating neurotransmitter vesicle dynamics. Keywords: late-onset Alzheimer disease, BIN1, Morris water maze, synaptic physiology, release probability, super-resolution, dSTORM, STED, 3D EM reconstruction, Amphiphysin 2http://www.sciencedirect.com/science/article/pii/S221112472030187X |