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Inhibition of neurite outgrowth following intracellular delivery of anti-GAP-43 antibodies depends upon culture conditions and method of neurite induction
Authors:T. B. Shea  L. I. Benowitz
Abstract:NB2a/dl neuroblastoma cells acquire a neuronal phenotype in response to several differentiating agents, including dibutyryl cAMP (dbcAMP) and the withdrawal of serum. As shown previously, antibodies to the growth-associated protein, GAP-43, introduced intracellularly using a lipid carrier, blocked the differentiation induced by dbcAMP. Antibodies to GAP43, at a low concentration, also blocked neurite out-growth induced by serum withdrawal when cells were grown on a relatively unadhesive substrate. On more adhesive substrates such as poly-L-lysine and laminin, however, anti-GAP-43 antibodies had less of an effect on neurite outgrowth. Previous studies have shown that the increased adhesivity of laminin allows a small but significant population of neurites to grow from serum-deprived cells, even in the presence of the microtubule-depolymerizing drug, colchicine. The outgrowth of this population of neurites was blocked by antibodies to GAP-43. These results are in conformity with recent studies showing that the requirement for GAP-43 in neuritogenesis may be related to membrane adhesiveness, and may contribute to an understanding of some of the apparent discrepancies in the literature concerning the involvement of GAP-43 in neuronal differentiation. © 1995 Wiley-Liss, Inc.
Keywords:GAP-43  neurite outgrowth  neuronal maturation  growth cone  extracellular matrix  laminin  adhesion
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