Compartmentalization of neuronal cytoskeletal proteins

The neuronal cytoskeJeton controls a myriad of functions in the adult and developing central nervous system including cell division, g rowth , m o t i l i t y , ce l lu la r shape, axonal and dendritic transport, neurosecretion, etc (1). The assembled fibrillar components of the neuronal cytoskeleton may be divided into microtubules (approx. 25 nm d iamete r )~ n e u r o f i l a m e n t s (approx. 10 nm diameter) , and microf i l a m e n t s (approx. 6 nm diameter) . Although microfilaments and mlc ro tubu l e s h a v e a ubiqui tous d i s t r ibu t ion in eukaryot ic ceils, neurofilaments are a class of intermediate filaments almost completely restricted to neurones. Protein analysis of these cytoskeletal structures show that c~ and 8 tubulin~ polypeptides of Mr 200 000, 155 000, and 68 000, and actin are the major components of microtubules, neurofilaments~ and microfilaments respectively. In addition to these major cytoskeletal proteins there are a variety of minor proteins that are associated with cytoskeletal elements (see Table 1), which may cross-link cytoskeletal proteins to each other or to cell structures and modi fy the polymerization of fibrillar structures from unassembled protein subunits. Such interactions may be controlled by e n z y m a t i c processes such as protein phosphorylation9 which has been shown to r egu l a t e the i n t e r a c t i o n of actin with the microtubule-associated protein MAP2 (2). It has become apparen t in recent years that cytoskeletal and associated proteins may exhibit considerable biochemical heterogeneity9 raising the possibility that cytoskeletai structures could be different between or within cells. The purpose of this review is to bring to the reader's at tention that these heterogeneous proteins show differential d i s t r ibu t ion within different neurones and within compartments of individual neurones . We shall not consider proteins that have a c y t o s k e l e t a l func t ion in the nervous system but are present in non-neuronal cell types (e.g. neuroglia). Since individual neurones and regions within neurones (e.g. axon/dendrite) may have specialized func t ions , we consider that eytoskeletal protein heterogeneity and c o m p a r t m e n t a l i z a t i o n may be impor t an t for functional diversity. Because much of the information we will present has come from immunocy tochemica l studies in the rat cerebellar cortex~ we have included a schematic diagram of the principal cell types to indicate