Although microRNA (miRNA) regulates gene expression inside the cell where they are transcribed, extracellular miRNA has been recently discovered outside the cells, proposing that miRNA might be released to participate in cell-to-cell communication (Front Endocrinol. 2017).

My group first reported the active exocytosis of miRNAs independently of exosomes in response to neuronal stimulation.

We propose a new function of non-coding RNAs named (‘ribomone’ = ribonucleotide + hormone), and suggest that miRNAs may function as hormones; i.e., miRNA is stored in vesicles and released by vesicle fusion in response to stimulation, thereby contributing to cell-to-cell communication.

Vesicles in neurons and neuroendocrine cells store neurotransmitters and peptide hormones, which are released by vesicle fusion in response to Ca2+‐evoking stimuli. Synaptotagmin‐1 (Syt1), a Ca2+ sensor, mediates ultrafast exocytosis in neurons and neuroendocrine cells.

The molecular mechanisms by which Syt1 triggers vesicle fusion remain controversial; six molecular models of Syt1 are summarized above (FEBS Lett. 2018).

We are investigating to unveil the novel mechanisms of vesicle fusion using synthetic neurotransmission that reconstitutes the vesicle fusion process with purified native vesicles, i.e., synaptic vesicles and large dense-core vesicles (LDCVs). Synthetic neurotransmission allows us to directly explore the mechanisms of vesicle fusion.

Use of neuronal differentiation of induced pluripotent stem cells (iPSC) as a disease model of autism and neurodegenerative disorders.

Some specific questions I wish to address are:

i) to identify functionally active iPSC-derived neurons using calcium imaging and patch clamp techniques.

ii) to examine that the mutation of ion channels related to autism is corrected by CRISPR-Cas9 and edited ion channels recover the ionic current in iPSC neurons as an autism model.