Delivery of anti-GAP-43 antibodies into neuroblastoma cells reduces growth cone size.
We have previously demonstrated that antibodies to the growth-associated protein, GAP-43, introduced intracellularly using a lipid carrier inhibited neurite outgrowth in NB2a/d1 neuroblastoma cells, and that culturing of these cells on adhesive substrates such as laminin or poly-L-lysine overcame this restriction. These findings suggest that GAP-43 may facilitate neuritogenesis by increasing membrane adhesiveness. To address this issue, in the present study we examined the effect of intracellular delivery of this antibody on growth cone size. A statistically significant percentage of those neurites that did elaborate following intracellular delivery of GAP-43 exhibited either no observable growth cones or smaller growth cones versus cells receiving pre-immune IgG. These results support the hypothesis that the requirement for GAP-43 in neuritogenesis may be related to growth cone formation and membrane adhesiveness.
Shea
T B
TB
Laboratory for Molecular Neuroscience, McLean Hospital, Belmont, MA 02178.
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D019922:GAP-43 Protein; D007074:Immunoglobulin G / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009447:Neuroblastoma; D016900:Neurofilament Proteins / Q000502:physiology; D011107:Polylysine / Q000494:pharmacology; D012756:Sheep / Q000276:immunology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D019922:GAP-43 Protein; D007074:Immunoglobulin G; D007797:Laminin; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D011107:Polylysine; D003994:Bucladesine