An influenza-derived membrane tension-modulating peptide regulates cell movement and morphology via actin remodeling

Toshihiro Masuda,Shiroh Futaki,Naoyuki Inagaki,Toshiki Itoh,Tomoka Takatani-Nakase,Takeshi Nomura,Kentarou Baba,Masahiro Sokabe,Tomo Murayama,Kazuya Tsujita

doi:10.1038/s42003-019-0486-3

Abstract

Tension in cell membranes is closely related to various cellular events, including cell movement and morphogenesis. Therefore, modulation of membrane tension can be a new approach for manipulating cellular events. Here, we show that an amphipathic peptide derived from the influenza M2 protein (M2[45–62]) yields lamellipodia at multiple sites in the cell. Effect of M2[45–62] on cell membrane tension was evaluated by optical tweezer. The membrane tension sensor protein FBP17 was involved in M2[45–62]-driven lamellipodium formation. Lysine-to-arginine substitution in M2[45–62] further enhanced its activity of lamellipodium formation. M2[45–62] had an ability to reduce cell motility, evaluated by scratch wound migration and transwell migration assays. An increase in neurite outgrowth was also observed after treatment with M2[45–62]. The above results suggest the potential of M2[45–62] to modulate cell movement and morphology by modulating cell membrane tension.

Highlights

Tension in cell membranes is closely related to various cellular events, including cell movement and morphogenesis
An involvement of the F-BAR domain protein FBP17 in this process was confirmed by siRNA knockdown—FBP17 has been known as a sensor of membrane curvature and was recently reported to have a role as a membrane tension sensor, translating cell membrane tension into cell movement (Fig. 1b, c
The M2[45–62] treatment tended to increase the number of neurites per neuron (Fig. 6d). These results clearly showed the ability of M2[45–62] to stimulate neurite outgrowth, which may accompany the decrease in cell membrane tension induced by the peptide and the eventual decrease in the tension barrier for actin polymerization

Summary

Introduction

Tension in cell membranes is closely related to various cellular events, including cell movement and morphogenesis. The importance of cell membrane tension in regulating cell movement and morphology has been reported, only approaches to use small-molecular-weight amphiphiles, including deoxycholic acid, have been reported to reduce cell membrane tension, but no approach by externally added peptides or proteins as long as we know Such peptides should have a great promise as a novel chemical tool to modulate cell function, with potential of conjugating other cellular or non-cellular functional proteins. We demonstrate that cell membrane tension was successfully modulated by a synthetic 18-residue peptide derived from the influenza M2 protein (amino acid positions 45–62) (M2 [45–62]) This peptide was obtained through the evaluation of the effect on actin organization. Morphological changes, including increased neurite outgrowth, in primary neuronal cultures were induced by treatment with M2[45–62] These results suggest promise for our peptidemediated approach to modulate cell movement and morphogenesis by affecting cell membrane tension

Methods

Results

Conclusion