As developing or regenerating neurons grow, their axons seek cues in the extracellular matrix that are recognized by integrin receptors. To understand the regulation and structure of neural integrin complexes, we have examined the association of two functionally important integrins, alpha 1 beta 1 and alpha 3 beta 1, within PC12 cells. Detergent-resistant cytoskeletal ghosts were prepared from PC12 cells and examined by immunoblotting. In cells maintained in suspension the alpha 1, alpha 3, and beta 1 integrin subunits were solubilized by Triton X-100 detergent. In contrast, when cells were grown on collagen or laminin about 50% of the alpha 1 and beta 1 subunits were retained with the cytoskeleton, but alpha 3 remained soluble. Confocal immunofluorescence microscopy of whole cells demonstrated that all three integrin subunits were expressed in a punctate pattern on the cell surface in point contacts. Point contacts were also found to be the predominant adhesion structure of dorsal root ganglion neurons. After detergent extraction of PC12 cells, the point contacts remained only at the cell-substrate interface. Vinculin, which is found consistently in focal contacts on non-neural cells, showed only a partial colocalization with the point contacts, being expressed mainly at the tips of filopodia and the periphery of cell bodies. Talin showed no obvious codistribution with beta 1 integrin immunoreactivity in point contacts. Immunoreactivity to p125FAK was not detected in PC12 cells, although astrocytes, which have both focal contacts and point contacts have p125FAK only at focal contacts. These observations, together with previous data (Turner et al., 1989; Tawil et al., 1993), suggest that point contacts are functional adhesion sites and are structurally distinct from focal contacts found in non-neuronal cells.