Developmental Cell
Volume 22, Issue 3, 13 March 2012, Pages 515-529
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Article
In Vivo Imaging of Molecular Interactions at Damaged Sarcolemma

https://doi.org/10.1016/j.devcel.2011.12.008Get rights and content
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Summary

Muscle cells have a remarkable capability to repair plasma membrane lesions. Mutations in dysferlin (dysf) are known to elicit a progressive myopathy in humans, probably due to impaired sarcolemmal repair. We show here that loss of Dysf and annexin A6 (Anxa6) function lead to myopathy in zebrafish. By use of high-resolution imaging of myofibers in intact animals, we reveal sequential phases in sarcolemmal repair. Initially, membrane vesicles enriched in Dysf together with cytoplasmic Anxa6 form a tight patch at the lesion independently of one another. In the subsequent steps, annexin A2a (Anxa2a) followed by annexin A1a (Anxa1a) accumulate at the patch; the recruitment of these annexins depends on Dysf and Anxa6. Thus, sarcolemmal repair relies on the ordered assembly of a protein-membrane scaffold. Moreover, we provide several lines of evidence that the membrane for sarcolemmal repair is derived from a specialized plasma membrane compartment.

Highlights

► Knockdown of dysferlin and annexin A6 leads to myopathy in zebrafish ► Sarcolemma is repaired by recruiting dysferlin-labeled plasma membrane compartments ► Dysferlin and annexin A6 generate an initial sarcolemmal repair patch ► Sequential recruitment of annexins to the patch depends on dysferlin and annexin A6

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Present address: Centre for Molecular and Cellular Biology of Inflammation, King's College London, New Hunts House, Guy's Campus, London SE1 1UL, UK