Directing traffic: MAPs, motors, and cellular logistics

Eukaryotic cells rely on long-range microtubule transport to accurately position mitochondria, and other organelles and vesicles with spatial and temporal precision. While kinesin and dynein motors drive directional movement, motor activity alone cannot explain the diversity and adaptability of organelle trafficking in vivo. Here, we synthesize recent evidence that non-motor microtubule-associated proteins (MAPs) convert microtubules into information-rich transport networks by decorating specific lattice subsets, modifying microtubule mechanics and controlling motor access and activation. Through steric filtering, modulation, or activation, MAPs impose motor-specific rules that shape transport efficiency and directionality. MAPs also couple trafficking to signaling by interacting with kinases, phosphatases, and receptors, and their dysregulation contributes to neurodegeneration and cancer, highlighting MAP-regulated transport as a therapeutic target.