Abstract
Laminin is a potent stimulator ofneurite outgrowth. We have examined the signal transduction events involved in the neuronal cell response to laminin. Cyclic nucleotides, calcium, and sodium‐proton exchange do not appear to be required for the transduction of the laminin signal during neurite outgrowth. Direct measurement of cAMP and cGMP levels shows no changes in NG108‐15 cells when cultured on laminin. Exogenous cAMP alone had no effect on either the rate of process formation or process length, but did alter the morphology of laminin‐induced neurites. A four‐fold increase in the number of branches per neurite and a two‐to‐three‐fold increase in the number of neurites per cell were observed in both NG108‐15 and PC12 cells cultured on laminin when either 8‐BrcAMP or forskolin was added. The cAMP‐induced branching was also observed when PC12 cells were cultured on a laminin‐derived synthetic peptide (PA22‐2), which contains the neurite‐promoting amino acid sequence IKVAV. By immunofluorescence analysis with axonal or dendritic markers, the PC12 processes on laminin and PA22‐2 were axonal, not dendritic, and the cAMP‐induced morphological changes were due to axonal branching. These data demonstrate that changes in cAMP are not involved in laminin‐mediated neurite outgrowth, but cAMP can modulate the effects of laminin.