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bioRxiv · 10.1101/154831

Spectrin is a mechanoresponsive protein shaping the architecture of intercellular invasion

Duan, R.·Kim, J. H.·Shilagardi, K.·Schiffhauer, E.·Son, S.·Lee, D.·Li, S.·Thomas, C.·Luo, T.·Fletcher, D. A.·Robinson, D. N.·Chen, E. H.
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Abstract

Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage1-3. Here, we report that spectrin dynamically accumulates and dissolves at the fusogenic synapse, where an attacking fusion partner mechanically invades its receiving partner with actin-propelled protrusions to promote cell-cell fusion4-7. Using genetics, cell biology, biophysics and mathematical modeling, we demonstrate that unlike myosin II that responds to dilation deformation, spectrin exhibits a mechanosensitive accumulation in response to shear deformation, which is highly elevated at the fusogenic synapse. The accumulated spectrin forms an uneven network, which functions as a \"sieve\" to constrict the invasive fingerlike protrusions, thus putting the fusogenic synapse under high mechanical tension to promote cell membrane fusion. Taken together, our study has revealed a previously unrecognized function of spectrin as a dynamic mechanoresponsive protein that shapes the architecture of intercellular invasion. These findings have general implications for understanding spectrin function in other dynamic cellular processes beyond cell-cell fusion.

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Duan, R., Kim, J. H., Shilagardi, K., Schiffhauer, E., Son, S., Lee, D., Li, S., Thomas, C., Luo, T., Fletcher, D. A., Robinson, D. N., Chen, E. H.. 2017-06-23. Spectrin is a mechanoresponsive protein shaping the architecture of intercellular invasion. https://doi.org/10.1101/154831

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