L1-dependent neuritogenesis involves ankyrin(B) that mediates L1-CAM coupling with retrograde actin flow

The cell adhesion molecule L1 (L1-CAM) plays critical roles in neurite growth. Its cytoplasmic domain (L1CD) binds to ankyrins that associate with the spectrin–actin network. This paper demonstrates that L1-CAM interactions with ankyrin(B) (but not with ankyrin(G)) are involved in the initial formation of neurites. In the membranous protrusions surrounding the soma before neuritogenesis, filamentous actin (F-actin) and ankyrin(B) continuously move toward the soma (retrograde flow). Bead-tracking experiments show that ankyrin(B) mediates L1-CAM coupling with retrograde F-actin flow in these perisomatic structures. Ligation of the L1-CAM ectodomain by an immobile substrate induces L1CD–ankyrin(B) binding and the formation of stationary ankyrin(B) clusters. Neurite initiation preferentially occurs at the site of these clusters. In contrast, ankyrin(B) is involved neither in L1-CAM coupling with F-actin flow in growth cones nor in L1-based neurite elongation. Our results indicate that ankyrin(B) promotes neurite initiation by acting as a component of the clutch module that transmits traction force generated by F-actin flow to the extracellular substrate via L1-CAM.