RRC ID 57200
Author Duan R, Kim JH, Shilagardi K, Schiffhauer ES, Lee DM, Son S, Li S, Thomas C, Luo T, Fletcher DA, Robinson DN, Chen EH.
Title Spectrin is a mechanoresponsive protein shaping fusogenic synapse architecture during myoblast fusion.
Journal Nat Cell Biol
Abstract 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.
Volume 20(6)
Pages 688-698
Published 2018-6-1
DOI 10.1038/s41556-018-0106-3
PII 10.1038/s41556-018-0106-3
PMID 29802406
PMC PMC6397639
MeSH Animals Animals, Genetically Modified Cell Fusion* Cell Line Cell Membrane / metabolism* Cell Membrane / ultrastructure Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Drosophila melanogaster / ultrastructure Mechanotransduction, Cellular* Membrane Fusion* Mice Microscopy, Fluorescence Models, Biological Myoblasts / metabolism* Myoblasts / ultrastructure Myoblasts, Skeletal / metabolism Spectrin / genetics Spectrin / metabolism* Stress, Mechanical Time Factors
IF 17.728
Times Cited 10