A novel role for the late-onset Alzheimer’s disease (LOAD)-associated protein Bin1 in regulating postsynaptic trafficking and glutamatergic signaling

Britta Schürmann, Daniel P. Bermingham, Katherine J. Kopeikina, Kristoffer Myczek, Sehyoun Yoon, Katherine E. Horan, Crystle J. Kelly, Maria Dolores Martin-de-Saavedra, Marc P. Forrest, Jessica M. Fawcett-Patel, Katharine R. Smith, Ruoqi Gao, Anthony Bach, Alain C. Burette, Joshua Zachary Rappoport, Richard J. Weinberg, Marco Martina, Peter Penzes*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Postsynaptic trafficking plays a key role in regulating synapse structure and function. While spiny excitatory synapses can be stable throughout adult life, their morphology and function is impaired in Alzheimer’s disease (AD). However, little is known about how AD risk genes impact synaptic function. Here we used structured superresolution illumination microscopy (SIM) to study the late-onset Alzheimer’s disease (LOAD) risk factor BIN1, and show that this protein is abundant in postsynaptic compartments, including spines. While postsynaptic Bin1 shows colocalization with clathrin, a major endocytic protein, it also colocalizes with the small GTPases Rab11 and Arf6, components of the exocytic pathway. Bin1 participates in protein complexes with Arf6 and GluA1, and manipulations of Bin1 lead to changes in spine morphology, AMPA receptor surface expression and trafficking, and AMPA receptor-mediated synaptic transmission. Our data provide new insights into the mesoscale architecture of postsynaptic trafficking compartments and their regulation by a major LOAD risk factor.

Original languageEnglish (US)
JournalMolecular Psychiatry
DOIs
StatePublished - Jan 1 2019

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Alzheimer Disease
AMPA Receptors
Synapses
Proteins
Spine
Clathrin
Monomeric GTP-Binding Proteins
Lighting
Synaptic Transmission
Microscopy
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Schürmann, Britta ; Bermingham, Daniel P. ; Kopeikina, Katherine J. ; Myczek, Kristoffer ; Yoon, Sehyoun ; Horan, Katherine E. ; Kelly, Crystle J. ; Martin-de-Saavedra, Maria Dolores ; Forrest, Marc P. ; Fawcett-Patel, Jessica M. ; Smith, Katharine R. ; Gao, Ruoqi ; Bach, Anthony ; Burette, Alain C. ; Rappoport, Joshua Zachary ; Weinberg, Richard J. ; Martina, Marco ; Penzes, Peter. / A novel role for the late-onset Alzheimer’s disease (LOAD)-associated protein Bin1 in regulating postsynaptic trafficking and glutamatergic signaling. In: Molecular Psychiatry. 2019.
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abstract = "Postsynaptic trafficking plays a key role in regulating synapse structure and function. While spiny excitatory synapses can be stable throughout adult life, their morphology and function is impaired in Alzheimer’s disease (AD). However, little is known about how AD risk genes impact synaptic function. Here we used structured superresolution illumination microscopy (SIM) to study the late-onset Alzheimer’s disease (LOAD) risk factor BIN1, and show that this protein is abundant in postsynaptic compartments, including spines. While postsynaptic Bin1 shows colocalization with clathrin, a major endocytic protein, it also colocalizes with the small GTPases Rab11 and Arf6, components of the exocytic pathway. Bin1 participates in protein complexes with Arf6 and GluA1, and manipulations of Bin1 lead to changes in spine morphology, AMPA receptor surface expression and trafficking, and AMPA receptor-mediated synaptic transmission. Our data provide new insights into the mesoscale architecture of postsynaptic trafficking compartments and their regulation by a major LOAD risk factor.",
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Schürmann, B, Bermingham, DP, Kopeikina, KJ, Myczek, K, Yoon, S, Horan, KE, Kelly, CJ, Martin-de-Saavedra, MD, Forrest, MP, Fawcett-Patel, JM, Smith, KR, Gao, R, Bach, A, Burette, AC, Rappoport, JZ, Weinberg, RJ, Martina, M & Penzes, P 2019, 'A novel role for the late-onset Alzheimer’s disease (LOAD)-associated protein Bin1 in regulating postsynaptic trafficking and glutamatergic signaling', Molecular Psychiatry. https://doi.org/10.1038/s41380-019-0407-3

A novel role for the late-onset Alzheimer’s disease (LOAD)-associated protein Bin1 in regulating postsynaptic trafficking and glutamatergic signaling. / Schürmann, Britta; Bermingham, Daniel P.; Kopeikina, Katherine J.; Myczek, Kristoffer; Yoon, Sehyoun; Horan, Katherine E.; Kelly, Crystle J.; Martin-de-Saavedra, Maria Dolores; Forrest, Marc P.; Fawcett-Patel, Jessica M.; Smith, Katharine R.; Gao, Ruoqi; Bach, Anthony; Burette, Alain C.; Rappoport, Joshua Zachary; Weinberg, Richard J.; Martina, Marco; Penzes, Peter.

In: Molecular Psychiatry, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Schürmann, Britta

AU - Bermingham, Daniel P.

AU - Kopeikina, Katherine J.

AU - Myczek, Kristoffer

AU - Yoon, Sehyoun

AU - Horan, Katherine E.

AU - Kelly, Crystle J.

AU - Martin-de-Saavedra, Maria Dolores

AU - Forrest, Marc P.

AU - Fawcett-Patel, Jessica M.

AU - Smith, Katharine R.

AU - Gao, Ruoqi

AU - Bach, Anthony

AU - Burette, Alain C.

AU - Rappoport, Joshua Zachary

AU - Weinberg, Richard J.

AU - Martina, Marco

AU - Penzes, Peter

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N2 - Postsynaptic trafficking plays a key role in regulating synapse structure and function. While spiny excitatory synapses can be stable throughout adult life, their morphology and function is impaired in Alzheimer’s disease (AD). However, little is known about how AD risk genes impact synaptic function. Here we used structured superresolution illumination microscopy (SIM) to study the late-onset Alzheimer’s disease (LOAD) risk factor BIN1, and show that this protein is abundant in postsynaptic compartments, including spines. While postsynaptic Bin1 shows colocalization with clathrin, a major endocytic protein, it also colocalizes with the small GTPases Rab11 and Arf6, components of the exocytic pathway. Bin1 participates in protein complexes with Arf6 and GluA1, and manipulations of Bin1 lead to changes in spine morphology, AMPA receptor surface expression and trafficking, and AMPA receptor-mediated synaptic transmission. Our data provide new insights into the mesoscale architecture of postsynaptic trafficking compartments and their regulation by a major LOAD risk factor.

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