Microtubule-associated proteins and neuronal morphogenesis

Abstract

Summary The microtubule-associated proteins (MAPs) are a set of structural proteins that bind to microtubules in vitro. Several of them occur at high levels in neurons where their expression is under strong developmental regulation, suggesting that they are involved in neuronal morphogenesis. Recently cDNAs for several of them have been cloned and sequenced revealing their primary structures and opening the way for genetic manipulation experiments aimed at determining their functions. Such experiments have shown that there are at least two classes of MAPs that are distinguished by the amino acid sequence motifs by which they bind to tubulin. One of these classes contains three known genes, two of which have been expressed in non-neuronal cells where the proteins cause bundling of microtubules and their rearrangement within the cytoplasm. The mechanism of this rearrangement is at present controversial. Another significant feature of these proteins is that several of them are differentially distributed within the neuronal cytoplasm; for example, some forms of MAP2 are selectively located in dendrites while in many situations MAP tau is limited to axons. In the case of MAP2, the mRNA that encodes the protein is also located in dendrites. This suggests that synthesis of MAP2 may be regulated locally in the dendritic cytoplasm. The molecular mechanism underlying the sorting of these proteins within neurons is unknown at present.