Neuronal Microtubule-associated Proteins: Insights into Their Structures and Functions

Two families of microtubule-associated proteins (MAPs), the MAP1 family and the MAP2/MAP4/tau superfamily, are found in neurons. This review describes the cellular and subcellular localizations, structural features, and in vitro properties of these MAP families. The MAP1 family consists of three members, MAP1A, MAP1B, and MAP1S. They not only show partial amino acid sequence homology, but also share a common structural property: each MAP1 polypeptide translated from the corresponding mRNA is proteolytically cleaved into two chains, which assemble into the mature MAP1 complex. MAP1A and MAP1B expression is complementary during neuronal development, and MAP1B malfunction disturbs axonal growth. The MAP1 family proteins not only bind to microtubules but also interact with other cellular components. The MAP2/MAP4/tau superfamily also consists of three members, MAP2, MAP4, and tau. They share highly homologous microtubule-binding sequences in their microtubule-binding domains, while the other domains that protrude from the microtubule surfaces are totally distinct among the family members. MAP2 is mainly localized in cell bodies and dendrites, while tau is concentrated in axons. A low content of MAP4 is evenly distributed in cell bodies, dendrites and axons. Multiple variants of MAP2, MAP4, and tauare generated through alternative splicing, which is regulated in developmental stage- and tissue-specific manners. The MAP2/MAP4/tau superfamily proteins are highly active in forming, stabilizing, and stiffening microtubules. The minimal essential domain common among the family members was deduced to include the carboxyl terminal part of the Pro-rich region and a couple of microtubule-binding sequence repeats.