Bundling and cross-linking of intermediate filaments of the nervous system

Ultrastructural studies have shown that neurons and glia in the mammalian nervous system contain bundles of often hundreds or more individual intermediate filaments. The means by which these bundles are formed and maintained has not been examined. We describe a series of simple experiments indicating that intermediate filament bundles derived from neuronal and glial processes are extremely stable, being resistant to a variety of extreme conditions. Furthermore, a preliminary examination of the mechanism of bundling for both types of filaments rules out several models for the production and control of cross-linking. We conclude that the long processes of both neurons and glia are stabilized by bundled intermediate filaments exhibiting strong interfilament interactions. We present a reconciliation these findings with previous data suggesting that neurofilaments are not actively cross-linked. We also describe a novel detergent-insoluble annular cytoskeletal structure, which appears to constrict bundles of axonal neurofilaments locally.