Spectrin is a mechanoresponsive protein shaping fusogenic synapse architecture during myoblast fusion

• DOI: 10.1038/s41556-018-0106-3
• Publication Date: 2018-05-22T08:49:32Z
• Authors: Rui Duan; Ji Hoon Kim; Khurts Shilagardi; Eric S. Schiffhauer; Donghoon M. Lee; Sungmin Son; Shuo Li; Claire Thomas; Tianzhi Luo; Daniel A. Fletcher; Douglas N. Robinson; Elizabeth H. Chen
• Keywords: 0303 health sciences; Time Factors; Myoblasts, Skeletal; Cell Membrane; Spectrin; Mechanotransduction, Cellular; Membrane Fusion; Models, Biological; Article; Cell Line; Animals, Genetically Modified; Cell Fusion; Myoblasts; Mice; 03 medical and health sciences; Drosophila melanogaster; Microscopy, Fluorescence; Animals; Drosophila Proteins; Stress, Mechanical

Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage. Here, we report that α/βH-spectrin (βH is also called karst) dynamically accumulates and dissolves at the fusogenic synapse between fusing Drosophila muscle cells, where an attacking fusion partner invades its receiving partner with actin-propelled protrusions to promote cell fusion. Using genetics, cell biology, biophysics and mathematical modelling, we demonstrate that spectrin exhibits a mechanosensitive accumulation in response to shear deformation, which is highly elevated at the fusogenic synapse. The transiently accumulated spectrin network functions as a cellular fence to restrict the diffusion of cell-adhesion molecules and a cellular sieve to constrict the invasive protrusions, thereby increasing the mechanical tension of the fusogenic synapse to promote cell membrane fusion. Our study reveals a function of spectrin as a mechanoresponsive protein and has general implications for understanding spectrin function in dynamic cellular processes.