Prof. Shiro Suetsugu - From BAR-domain-mediated membrane shaping to the transfer of the cytoplasmic proteins between cells - IPBS-Toulouse, Seminar Room

Shiro Suetsugu

Nara Institute of Science and Technology, Nara, Japan

From BAR-domain-mediated membrane shaping to the transfer of the cytoplasmic proteins between cells: efficiency of protein transfer through protrusion-derived extracellular vesicles

Extracellular vesicles (EVs) are lipid membrane-bound vesicles facilitating the transfer of proteins, RNAs, lipids, and other cellular materials between cells. They are primarily classified into endosome-derived EVs (exosomes) and plasma membrane protrusion-derived EVs (ectosomes). Our key focus in EV research is the role of the Bin-Amphiphysin-Rvs (BAR) domain superfamily proteins, which are crucial for plasma membrane deformation during endocytosis for the generation of endocytic vesicles and membrane protrusion formation for filopodia and protrusion-derived vesicles. The inverse BAR (I-BAR) domain-containing proteins, such as Missing-in-Metastasis (MIM), regulate membrane protrusion formation. Notably, MIM-dependent protrusion-derived EVs have been identified to contain Rac1, a small GTPase that promotes cell migration. Our study provides direct evidence that Rac1 within MIM-dependent EVs is delivered from endosomes into the cytoplasm of recipient cells, inducing cellular migration. Importantly, the research highlights that engineered MIM-dependent protrusion-derived EVs can efficiently deliver the genome-editing protein Cas12f to recipient cells. Unlike endosome-derived EVs, these protrusion-derived EVs achieve high delivery efficiency, positioning them as promising next-generation biomolecular delivery platforms.

Selected publications

• D'Angelo G et al. Protrusion-derived vesicles: new subtype of EVs? Nat Rev Mol Cell Biol 2023 24(2):81-82
• Wan Mohamad Noor WNI et al. Small GTPase Cdc42, WASP, and scaffold proteins for higher-order assembly of the F-BAR domain protein. Sci Adv 2023 28;9(17)