Annexins cooperate with Myomaker to promote myoblast fusion.

Annexins A2, A5, and A6 cooperate with Myomaker at the myoblast plasma membrane to promote myoblast fusion, with simultaneous knockdown impairing fusion.

• Why it matters: Myomaker is indispensable for myoblast fusion, but how its short extracellular domain works with other proteins to drive membrane fusion remains unclear.
• What they did: Using an APEX2-based proximity labeling screen in a synchronized myoblast fusion and differentiation system, compared against a fusion-deficient Myomaker mutant, Annexins A2/A5/A6 were identified and colocalized with Myomaker; proximity ligation assays confirmed cell-surface association.
• The result: Annexins A2, A5, and A6 promoted heterologous fibroblast–myoblast fusion, and while single knockdown had minimal effects, simultaneous knockdown of all three impaired myoblast fusion, indicating redundancy.