The Ig Superfamily Cell Adhesion Molecule, apCAM, Mediates Growth Cone Steering by Substrate–Cytoskeletal Coupling
| Autor: | Paul Forscher, Laura D. Errante, Daniel M. Suter, Victoria Belotserkovsky |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Microtubules
Polymerase Chain Reaction Models Biological 03 medical and health sciences 0302 clinical medicine Tubulin Cell Movement Microtubule Aplysia Cell Adhesion Animals Cloning Molecular Cytoskeleton Growth cone Cells Cultured Actin DNA Primers 030304 developmental biology Neurons 0303 health sciences Microscopy Video biology Cell adhesion molecule Fishes Cell Biology Silicon Dioxide Actin cytoskeleton Actins Recombinant Proteins Ganglia Invertebrate Cell biology Kinetics Connective Tissue Immunoglobulin G Commentary biology.protein Immunoglobulin superfamily Stress Mechanical Cell Adhesion Molecules 030217 neurology & neurosurgery Regular Articles |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.141.1.227 |
| Popis: | Dynamic cytoskeletal rearrangements are involved in neuronal growth cone motility and guidance. To investigate how cell surface receptors translate guidance cue recognition into these cytoskeletal changes, we developed a novel in vitro assay where beads, coated with antibodies to the immunoglobulin superfamily cell adhesion molecule apCAM or with purified native apCAM, replaced cellular substrates. These beads associated with retrograde F-actin flow, but in contrast to previous studies, were then physically restrained with a microneedle to simulate interactions with noncompliant cellular substrates. After a latency period of ∼10 min, we observed an abrupt increase in bead-restraining tension accompanied by direct extension of the microtubule-rich central domain toward sites of apCAM bead binding. Most importantly, we found that retrograde F-actin flow was attenuated only after restraining tension had increased and only in the bead interaction axis where preferential microtubule extension occurred. These cytoskeletal and structural changes are very similar to those reported for growth cone interactions with physiological targets. Immunolocalization using an antibody against the cytoplasmic domain of apCAM revealed accumulation of the transmembrane isoform of apCAM around bead-binding sites. Our results provide direct evidence for a mechanical continuum from apCAM bead substrates through the peripheral domain to the central cytoplasmic domain. By modulating functional linkage to the underlying actin cytoskeleton, cell surface receptors such as apCAM appear to enable the application of tensioning forces to extracellular substrates, providing a mechanism for transducing retrograde flow into guided growth cone movement. |
| Databáze: | OpenAIRE |
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