Recently, a great deal of interest has been focused on the cytoskeletal basis of neuronal development and regeneration. In this review, we outline what is currently known about the role of the cytoskeletal proteins, particularly microtubule-associated proteins tau and MAP1B, in the growth cone translocation. Second, we describe in more detail the tau gene organization and developmental regulation, and tau protein structure. Finally, we discuss how the posttranslational modifications of tau proteins, particularly phosphorylation, modulate its roles in establishment of axonal polarity, morphology and outgrowth. It seems that it takes about 20-30 years from the earliest neuronal changes caused by light hyperphosphorylation of tau proteins to the development of obvious symptoms of Alzheimer's disease, because such neurons are only visible in adults over 30. Although it has become evident that tau is highly phosphorylated in the developing brain in a manner similar to the phosphorylation state in Alzheimer's disease, the precise roles of microtubule-associated fetal kinases and their respective epitopes in this process have yet to be elucidated. |