Research (Hiroko Bannai)

Scope of our research

The brain, which processes vast amounts of information, is often compared to a computer. However, the brain is very different from a computer: in the brain, the proteins and lipids that make up the brain are constantly being replaced throughout life. How can the brain maintain its structure and perform higher functions such as memory, learning, and thinking while its components are constantly being replaced? Although it is believed that mutations in genes and proteins cause Alzheimer's disease and other neurological disorders, it is still unclear why these mutations cause severe symptoms. Our laboratory aims to elucidate the mechanisms of memory and learning and the pathogenesis of neurological diseases such as epilepsy, and Alzheimer's disease, by "Watching" the structure, function, and dynamics of the protein molecules that make up the living body in living cells.

Our research activities include

(1) "Physiological research": to understand the molecular mechanism of the development, maintenance, and regulation of the synapses, which are the basis of learning of memory, we visualize the behavior and the localization of synaptic molecules in live neurons.

(2) "Pathological research": to clarify the pathogenic mechanism of neurological disorders such as Alzheimer's disease and Parkinson's disease, we examine the effect of pathological Tau, Amyloid β, and αSynuclein on the synaptic structure and function.

(3) "Research for the development of new technologies" to visualize and manipulate biological molecules in living cells, we develop new experimental tools that are based on the latest findings in biophysics.

How do we "watch" the behavior of molecules?

QD-SPT: A powerful tool to visualize the molecular dynamics

According to the fluid mosaic model, plasma membrane molecules such as lipids and transmembrane proteins have the ability to undergo lateral diffusion freely throughout the cell. In some cell types, however, specific membrane molecules are concentrated in cellular microdomains, by overcoming the randomizing effects of free diffusion. This polarized distribution of membrane molecules is crucial for various cell functions, thus it is important to understand the mechanism through which the cell regulates the lateral diffusion of membrane molecules.

Quantum-dot single particle tracking (QD-SPT), a single molecule imaging technique using semiconductor nanocrystal quantum dots as a fluorescent probe, is a powerful tool to analyze the behavior of proteins and lipids on the plasma membrane. QD-SPT experiments that allowed us to obtain further insights into the strategy and physiological relevance of membrane self-organization in neurons and astrocytes, two major component cells in the brain.

What does membrane dynamics tell us?

Single-molecule resolution imaging has highlighted the existence and importance of self-organization mechanisms in neurons and glia. Additionally, a growing body of evidence demonstrates that neuronal and glial receptor dynamics become abnormal in disease states. Altered molecular diffusion dynamics comprise an important pathological phenotype.

Featured Publications

Bannai H, Lévi S, Schweizer C, Dahan M, *Triller A. “Imaging the lateral diffusion of membrane molecules with quantum dots.”
Nature Protocols 1:2628-2634. (2006)
http://www.nature.com/nprot/journal/v1/n6/full/nprot.2006.429.html

Bannai H, Lévi S, Schweizer C, Inoue T, Launey T. Racine V, Sibarita J.B, Mikoshiba K, Triller A.
“Activity-Dependent Tuning of Inhibitory Neurotransmission Based on GABAAR Diffusion Dynamics”
Neuron 62:670-682. (2009)
http://www.sciencedirect.com/science/article/pii/S089662730900347X

Arizono M, *Bannai H, Nakamura K, Niwa F, Enomoto M, Matsu-Ura T, Miyamoto A, Sherwood MW, Nakamura T, *Mikoshiba K. “Receptor-selective diffusion barrier enhances sensitivity of astrocytic processes to metabotropic glutamate receptor stimulation.”
Science Signaling 5: ra27. (2012)
http://stke.sciencemag.org/content/5/218/ra27

Bannai H1 Niwa F1 Sherwood MW, Shrivastava AN, Arizono M, Miyamoto A, Sugiura K, Lévi S, Triller A*, Mikoshiba K*. (1: co-first author) “Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium”
Cell Reports, 13: 2768-2780 (2015)
http://www.cell.com/cell-reports/abstract/S2211-1247(15)01414-X

Bannai H, Inoue T, Hirose M, Niwa F, Mikoshiba K "Synaptic Function and Neuropathological Disease Revealed by Quantum Dot-Single-Particle Tracking"

Neuromethods 131-155 (2020)
https://link.springer.com/protocol/10.1007/978-1-0716-0532-5_7

REVIEW Article

*Bannai H
"Molecular membrane dynamics: Insights into synaptic function and neuropathological disease"
Neuroscience Resaerch, 129: 47-56 (2018) * Selected for Cover
https://www.sciencedirect.com/science/article/pii/S0168010217302274

*Bannai H, Niwa F, Sakuragi S, Mikoshiba K.
Inhibitory synaptic transmission tuned by Ca2+ and glutamate through the control of GABAA R lateral diffusion dynamics.Dev Growth Differ. 62(6):398-406.(2020)
https://onlinelibrary.wiley.com/doi/full/10.1111/dgd.12667

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