Ankyrin binding mediates L1CAM interactions with static components of the cytoskeleton and inhibits retrograde movement of L1CAM on the cell surface

Dept. of Pharmacology and Biological Chemistry, Box 1215, One Gustave L. Levy Place, Mt. Sinai School of Medicine, New York, NY 10029, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 09/2003; 162(4):719-30. DOI: 10.1083/jcb.200211011
Source: PubMed

ABSTRACT The function of adhesion receptors in both cell adhesion and migration depends critically on interactions with the cytoskeleton. During cell adhesion, cytoskeletal interactions stabilize receptors to strengthen adhesive contacts. In contrast, during cell migration, adhesion proteins are believed to interact with dynamic components of the cytoskeleton, permitting the transmission of traction forces through the receptor to the extracellular environment. The L1 cell adhesion molecule (L1CAM), a member of the Ig superfamily, plays a crucial role in both the migration of neuronal growth cones and the static adhesion between neighboring axons. To understand the basis of L1CAM function in adhesion and migration, we quantified directly the diffusion characteristics of L1CAM on the upper surface of ND-7 neuroblastoma hybrid cells as an indication of receptor-cytoskeleton interactions. We find that cell surface L1CAM engages in diffusion, retrograde movement, and stationary behavior, consistent with interactions between L1CAM and two populations of cytoskeleton proteins. We provide evidence that the cytoskeletal adaptor protein ankyrin mediates stationary behavior while inhibiting the actin-dependent retrograde movement of L1CAM. Moreover, inhibitors of L1CAM-ankyrin interactions promote L1CAM-mediated axon growth. Together, these results suggest that ankyrin binding plays a crucial role in the anti-coordinate regulation of L1CAM-mediated adhesion and migration.

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Available from: Dan P Felsenfeld, Oct 28, 2014
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    • "Some insight into the mechanism of ethanol action in cortical axons may be provided by our data, which show that neurons growing on an L1CAM substrate are resistant to ethanolmediated silencing of growth cone responses to guidance cues. L1CAM is highly abundant and natively distributed in both raft and non-raft domains (Kamiguchi et al, 2000; IC and DLB, unpublished observations), and can be stably anchored to actin via ankyrin (Bennett and Lambert, 1999; Gil et al, 2003). Such anchored transmembrane proteins have been proposed to stabilize and organize plasma membrane by generating compartment boundaries and by limiting protein and lipid diffusion (Kusumi et al, 2005). "
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    • "Interestingly, the ankG– Nav1 interaction is regulated by CK2 phosphorylation, and the restriction of CK2 to the AIS can explain why Nav1 channels are preferentially trapped by ankG at the AIS rather than by ankB further down the axon (Bréchet et al., 2008). Ankyrinbased trapping of L1CAM by ankB has been demonstrated in axonal growth cones (Gil et al., 2003) and is also dependent on "
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    • "When L1 is bound to ankyrin, it shows little diffusion in the plasma membrane (Garver et al. 1997). If it is not bound to ankyrin, it can bind to retrograde actin flow and participate in powering growth cone advance (Gil et al. 2003). L1 bound to ankyrin is likely not available for endocytosis. "
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