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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)688-698
Number of pages11
JournalNature Cell Biology
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2018

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Spectrin
Myoblasts
Synapses
Cell Fusion
Proteins
Biophysics
Membrane Fusion
Cell Shape
Cell Adhesion Molecules
Muscle Cells
Drosophila
Cell Biology
Actins
Membrane Proteins
Cell Membrane

ASJC Scopus subject areas

  • Cell Biology

Cite this

Spectrin is a mechanoresponsive protein shaping fusogenic synapse architecture during myoblast fusion. / Duan, Rui; Kim, Ji Hoon; Shilagardi, Khurts; Schiffhauer, Eric S.; Lee, Donghoon M.; Son, Sungmin; Li, Shuo; Thomas, Claire; Luo, Tianzhi; Fletcher, Daniel A.; Robinson, Douglas N.; Chen, Elizabeth H.

In: Nature Cell Biology, Vol. 20, No. 6, 01.06.2018, p. 688-698.

Research output: Contribution to journalArticle

Duan, R, Kim, JH, Shilagardi, K, Schiffhauer, ES, Lee, DM, Son, S, Li, S, Thomas, C, Luo, T, Fletcher, DA, Robinson, DN & Chen, EH 2018, 'Spectrin is a mechanoresponsive protein shaping fusogenic synapse architecture during myoblast fusion', Nature Cell Biology, vol. 20, no. 6, pp. 688-698. https://doi.org/10.1038/s41556-018-0106-3
Duan, Rui ; Kim, Ji Hoon ; Shilagardi, Khurts ; Schiffhauer, Eric S. ; Lee, Donghoon M. ; Son, Sungmin ; Li, Shuo ; Thomas, Claire ; Luo, Tianzhi ; Fletcher, Daniel A. ; Robinson, Douglas N. ; Chen, Elizabeth H. / Spectrin is a mechanoresponsive protein shaping fusogenic synapse architecture during myoblast fusion. In: Nature Cell Biology. 2018 ; Vol. 20, No. 6. pp. 688-698.
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