Roland Brandt

Institute of Neurobiology, University of Heidelberg, INF 364, 69120 Heidelberg, Germany.

Received 05/21/96; Accepted 07/05/96; On-line 08/01/96

Neurons are one of the most extreme cell types in that they contain processes which can reach a meter or longer and encompass more than 99% of the cellular volume. This requires the presence of a sophisticated molecular machinery in order to establish and maintain such a morphology. From electron microscopic studies, it had been inferred that an extensive array of linear polymers confers the stability of the processes and is required for their formation. It became increasingly clear from the three cytoskeletal elements capable of forming such an array - actin filaments, intermediate filaments, and microtubules - that microtubules had a very important role due to their abundance in neurons, their characteristic morphological and biochemical organization during neuronal development, and their highly dynamic behavior (reviewed in (1)).

The assembly of microtubules is regulated largely by microtubule-associated proteins (MAPs). The neuronal MAPs, tau and MAP2, have attracted particular interest due to their polar distribution in the axonal versus somatodendritic compartment and, mainly in the case of tau, for its potential role in some neurodegenerative disorders (for reviews see ref. 2-5).

The focus of this review will be on the role of tau in neuronal development and process formation. First, studies on the molecular structure and functional organization of tau with respect to its activity to promote microtubule assembly and stability will be reviewed. Next, studies on the subcellular localization of tau in situ and in neuronal culture will be summarized. Then, apparently contradictory results on the role of tau obtained through gene-knockout and gene-transfer techniques will be discussed. In the final section of this review, increasing evidence for a role of tau beyond its function in promotion of microtubule assembly will be presented.