Figure 9.

Models for NrCAM mobility in the cell membrane modulated through interactions with the cytoplasmic region and raft-partitioning. TAG-1 beads (black) bind NrCAM receptors (green). Patches of receptors are stabilized within lipid rafts (blue circle on the membrane) and the cytoplasmic tail interacts with the actin cytoskeleton (red) via adaptors (yellow or blue). (A) Retrograde mobility of the TAG-1 bead under control condition. The bead recruits a high density of NrCAM receptors. Under the bead, NrCAM cytoplasmic domains are associated to rearward flowing actin filaments. This coupling occurs via unknown adaptors (yellow). (B) TAG-1 bead on NrCAM after cytochalasin D treatment. Actin bund-les are depolymerized. NrCAM coupling to remnant subcortical cytoskeletal network may account for the limited mobility of the bead. (C) Stationary behavior on NrCAMΔfnΔCter. TAG-1 bead is resistant to displacement by the laser trap. The C-terminal part of the NrCAM cytoplasmic tail is required for the coupling with the actin retrograde flow. In this condition, the highly reduced mobility of the bead may reflect the linkage of the proximal region of the cytoplamic tail to static subcortical actin filaments via adaptors (blue). (D) TAG-1 bead on NrCAMΔfnΔcyt. NrCAM is unable to interact directly to the cytoskeleton. The bead displays a reduced mobility and can be displaced by the laser trap. This immobile behavior altered by MBCD treatment, depends on the partitioning of NrCAM within a bead-induced stabilized raft. (E) TAG-1 bead on NrCAM after MBCD treatment. Coupling of NrCAM with the actin retrograde flow is prevented. The bead displays a stationary behavior and resists to the laser trap displacement. Disruption of rafts by MBCD impairs NrCAM clustering and the receptor avidity for its ligand is reduced. The density of NrCAM molecules under the bead may be too low to permit clutching with the actin retrograde flowing. The stationary behavior is due to interaction of the cytoplasmic tail with the subcortical actin.