MAP-1B TAU FUNCTIONAL REDUNDANCY DURING LAMININ-ENHANCED AXONAL GROWTH/

When cultured cerebellar macroneurons develop attached to a laminin-co ntaining substrate or after the acute addition of laminin to the tissu e culture medium, there is an acceleration in the rate and extent of a xonal elongation. Furthermore, laminin is capable of inducing axonal f ormation and microtubule stabilization in neurons arrested at stage II of neuritic development by tau suppression (Caceres and Kosik, 1990; Caceres et al., 1991), Laminin-enhanced or induced axonal extension is paralleled by a selective and dramatic incorporation of phosphorylate d MAP-1b into axonal microtubules, Axonal formation in neurons growing in the presence of laminin is prevented by treatment of the cultures with a mixture of MAP-1b and tau antisense oligonucleotides, but not b y the single suppression of any one of these MAPs. However, suppressio n of MAP-1b, but not of tau, greatly reduces the increase ire the rate and extent of axonal elongation induced by laminin, No such effects a re elicited by MAP-1b antisense oligonucleotides in neurons growing in the absence of laminin, e.g. polylysine alone, where most of the MAP- 1b present in the cells is dephosphorylated and not associated with th e cytoskeleton. Taken collectively, these data suggest that, with rega rd to axonal elongation, MAP-1b and tau can be functionally substitute d, and that extracellular matrix molecules, such as laminin, affect ax onal extension by promoting the in vivo utilization of MAP-1b.