Myoblasts fail to fuse if they lack the mannose receptor (bottom).

If myoblasts are to fuse with nascent myotubes and thus form muscles, they must apparently migrate and chew up extracellular matrix (ECM), according to Jansen and Pavlath (page 403). These activities require expression of the mannose receptor (MR) in differentiating myoblasts.

The pathway is induced when nascent myotubes secrete IL-4, which induced expression of the MR in myoblasts. Although MR-null myoblasts fused normally with other myoblasts, they were retarded in their ability to fuse with nascent myotubes, which is the second stage of myotube formation.

MR expression appears to be required in vivo as well as in vitro for normal myotube formation, as the myofibers in MR-null mice were smaller than those in wild-type animals.

The researchers found that MR-null myoblasts migrated more slowly than wild-type cells in response to chemotactic stimuli. Moreover, the mutant cells internalized less collagen than control cells, indicating that MR, which is an endocytic receptor, is required for efficient clearance of the ECM during cell movement.

Jansen and Pavlath note that MR activity is required for other cell fusion events, but its role in migration and ECM remodeling has not been reported previously. Another member of the MR family, Endo180, is also involved in cell migration and ECM clearance. Therefore, these activities might be a common function for the receptor family.