An Aplysia cell adhesion molecule associated with site-directed actin filament assembly in neuronal growth cones.
During neuronal growth cone-target interactions, a programmed sequence of cytoskeletal remodeling has been described, involving increased actin assembly at the target site and directed microtubule extension into it. The cell adhesion protein apCAM rapidly accumulates at such interaction sites, suggesting a possible role in regulating cytoskeletal remodeling. To test this hypothesis we crosslinked apCAM to varying degrees with antibodies. Secondary immunocomplexes exhibited a classical patching and capping response; in contrast, high density crosslinking of apCAM by antibody coated beads triggered localized actin assembly accompanied by formation of tail-like actin structures referred to as inductopodia. When beads were derivatized with increasing amounts of anti-apCAM they displayed three sequential dose-dependent kinetic states after binding: (1) lateral diffusion in the plane of the membrane; (2) restricted diffusion due to coupling with underlying F-actin; and (3) translocation in the plane of the membrane driven by de novo actin filament assembly local to bead binding sites, i.e. inductopodia formation. In contrast, lectin coated beads were far less efficient in triggering inductopodia formation despite demonstrated membrane protein binding. This work provides evidence that crosslinking of a diffusable membrane protein, apCAM, to threshold levels, can trigger highly localized actin filament assembly and rapid remodeling of neuronal cytoarchitecture.
Thompson
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Department of Cell Biology, Yale University, New Haven CT 06510, USA.
Lin
C H
CH
Forscher
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D000199:Actins / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D001048:Aplysia / Q000254:growth & development*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D009474:Neurons / Q000648:ultrastructure*
D000199:Actins; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules