The role of endocytic L1 trafficking in polarized adhesion and migration of nerve growth cones
| Autor: | Hiroyuki Kamiguchi, Fumie Yoshihara |
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| Předmět: |
genetic structures
Neurite Swine Recombinant Fusion Proteins Growth Cones Endocytic cycle Chick Embryo Biology Endocytosis Antibodies Adaptor Protein Complex alpha Subunits Ganglia Spinal Cell Adhesion Neurites Animals Humans ARTICLE Growth cone Cell adhesion Neural Cell Adhesion Molecules Cells Cultured Neurons Membrane Glycoproteins Cell adhesion molecule General Neuroscience Cell Polarity Membrane Proteins Adhesion Immunoglobulin Fc Fragments Rats Cell biology Protein Transport COS Cells Neural cell adhesion molecule sense organs Carrier Proteins Leukocyte L1 Antigen Complex |
| Zdroj: | ResearcherID |
| Popis: | Motility of the nerve growth cone is highly dependent on its dynamic interactions with the microenvironment mediated by cell adhesion molecules (CAMs). These adhesive interactions can be spatially regulated by changing the density and avidity of CAMs on the growth cone. Previous studies have shown that L1, a member of the immunoglobulin superfamily of CAMs, is endocytosed at the central domain of the growth cone followed by centrifugal vesicular transport and reinsertion into the plasma membrane of the leading edge. The present paper focuses on the functional significance of endocytic L1 trafficking in dorsal root ganglia neurons in vitro. We demonstrate that the rate of L1-based neurite growth has a positive correlation with the amount of endocytosed L1 in the growth cone, whereas stimulation of neurite growth via an N-cadherin-dependent mechanism does not increase L1 endocytosis. A growth cone that migrates on an L1 substrate exhibits a steep gradient of L1-mediated adhesion (strong adhesion at the growth cone's leading edge and weak adhesion at the central domain). This gradient of L1 adhesion is attenuated after inhibition of L1 endocytosis in the growth cone by intracellular loading of a function-blocking antibody against alpha-adaptin, a subunit of the clathrin-associated AP-2 adaptor. Inhibition of L1 endocytosis by this antibody also decreased the rate of L1-dependent growth cone migration. These results indicate that the growth cone actively translocates CAMs to create spatial asymmetry in adhesive interactions with its environment and that this spatial asymmetry is important for growth cone migration. |
| Databáze: | OpenAIRE |
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