Cytoskeleton (Hoboken) 2025 Jul 10; doi: 10.1002/cm.70000.

Perspective: Examining MAP1B Structure With an Evolutionary Perspective.

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Microtubule Associated Protein MAP1B is expressed at high levels during the early development of the nervous system, playing important roles in axonal growth, neuronal migration, and branching, as well as dendritic spine morphogenesis and synapse formation. MAP1B belongs to the MAP1 family, which includes MAP1A and MAP1S, as well as a known homolog in Drosophila (the Futsch gene). MAP1B is a polyprotein that undergoes proteolytic processing into heavy (HC) and light chains (LC1). It is composed of seven exons, including microtubule- and actin-binding domains, and conserved regions of both the N- and C-termini. In this Perspective, we investigated the structure of MAP1B from an evolutionary perspective, emphasizing the significance of conserved domains across different species. Through sequence analysis and alignment, exon structures, prediction of protein folding, and database searches, we identified key structural features of MAP1B and constructed a model based on these data. This approach allowed us to refine our understanding of known domains and uncover unrecognized, highly conserved domains that may have novel functions, providing valuable reference data for future research. In the process of searching for homolog proteins in vertebrates and invertebrates, we traced the deep roots of MAP1B as far back as the octopus, sea urchin, and Caenorhabditis elegans, underscoring the highly conserved properties of MAP1B. When compared to the other members of the MAP1 family, MAP1A and MAP1S, we found that they are far less conserved than MAP1B, even among vertebrates, supporting the conclusion that MAP1B represents the most ancient ancestral member of this family.

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