Phase separation on microtubules: from droplet formation to cellular function?

Microtubules are cytoskeletal polymers that play important roles in numerous cellular processes, ranging from the control of cell shape and polarity to cell division and intracellular transport. Many of these roles rely on proteins that bind to microtubule ends and shafts, carry intrinsically disordered regions, and form complex multivalent interaction networks. A flurry of recent studies demonstrated that these properties allow diverse microtubule-binding proteins to undergo liquid–liquid phase separation (LLPS) in vitro. It is proposed that LLPS could potentially affect multiple microtubule-related processes, such as microtubule nucleation, control of microtubule dynamics and organization, and microtubule-based transport. Here, we discuss the evidence in favor and against the occurrence of LLPS and its functional significance for microtubule-based processes in cells.