Stop and go L1CAM

杨柳

A mobile adhesion receptor allows a cell to migrate, whereas a stationary version of the same receptor keeps it in place, based on results from Gil et al. on page 719.+ u3 m4 d+ L, Y' p8 K# }5 P  p) U
, \2 P- e, `5 |# `) [
The immunoglobulin family member L1CAM promotes both growth cone extension in the developing central nervous system and cell adhesion-mediated maintenance of axon bundles in mature neurons. How the same adhesion molecule regulates these disparate functions is not clear, particularly since the L1 family does not undergo the class switching (from adhesion-promoter to migration-promoter) that seems to be common in integrins.* n& ]+ c! ~. s# E6 E3 C, f

: j4 a- `' O( g' G# }3 sRather than changing receptor types, L1CAM switches its own kinetic behavior to modulate cell movements. Stationary L1CAM, which may be associated with adhesion, was found to depend on ankyrin to stay in place. Release of the ankyrin linkage, either with a peptide derived from the L1CAM cytoplasmic tail or via growth factors that phosphorylate the tail,increased the amount of L1CAM moving back along the upper surface of the cell. This retrograde movement depends on dynamic actin pools and is reminiscent of vesicles on treadmilling actin. The direction of retrograde receptor movement seen on the upper surface of the cell is thought to reflect the direction of traction forces generated on the lower surface. In support of this theory, the authors found that peptide-mediated release of stationary L1CAM produced greater neurite extension through growth cone migration./ L* e, ^; l4 F; O' H; d

' H- B3 }+ F, S' S5 NDuring development, neurons may switch from migration in the growth cone to adhesion in the axon and synapse by increasingly dephosphorylating L1CAM (and therefore promoting ankyrin binding). L1CAM–ankyrin interactions may also be dynamically regulated in the growth cone to suppress traction forces that are incorrectly oriented. Peptides that interfere with L1CAM–ankyrin binding may one day be used therapeutically to awaken the retrograde movement of stationary L1CAM receptors in injured nerves.(L1CAM (green) interactions with ankyrin )