News from the Physiology Course: 91לPile-Up91ם of Proteins at Microtubule Ends Helps Scaffold the Cell

A recent study in got a big push from participants in the MBL Physiology course -- and draws upon MBL discoveries that go back for decades.
The paper concerns microtubules, the stiff filaments inside cells 91לthat are analogous to rigid 2 x 4s that hold up the cell,91ם says , a co-author on the paper who was a student in the 2017 Physiology course from Princeton University.
91לWe had previously observed that the tips of microtubules seemed to be coated with a sort of protein 91טglue91י that would cause them to stick to the membrane of the cell,91ם says King. 91לOr to extend the analogy, to allow the 2 x 4s to adhere to the house91יs roof.91ם
But what exactly was happening here?
In their paper, the team works out a physical description of how three proteins accumulate on the tip of a microtubule. These tip proteins, they discovered, are actually a collective material, 91לan association of proteins that aren91יt present in fixed ratios, but come about from multivalent interactions,91ם says of Delft University of Technology, the paper91יs senior author and a faculty member in 2017 Physiology.
And it91יs a motor protein that drives proteins to the tip, where they pile up. (Motor proteins were co-discovered by and others at the MBL in the mid-1980s).
91לWe cannot explain the observed network theoretically without this 'pile-up',91ם King says.
"Like a Huge Dollop of Glue"
Dogterom had come to the MBL Physiology course with the observation that the three microtubule tip proteins (Mal3, Tea2 and the aptly named Tip1) could be collectively transferred from a microtubule to a cell-membrane mimic.
91לWe found this observation puzzling because it suggested that those proteins collectively constitute a material,91ם King says.
King was then a PhD candidate at Princeton studying phase separation processes in cells with and , both of whom have long associations with MBL as faculty and investigators. Phase separation, in which molecules spontaneously form liquid-like droplets inside cells, was first observed in the 2008 Physiology course.
King teamed up in the course with Louis Reese, a post-doc from Dogterom91יs lab, to investigate. They decided to increase crowding to pack the tip proteins closer together.
91לUnder these conditions, the tip structure got bigger; in fact, it resembled a liquid-like droplet 91ד like when a kid defies their art teacher and puts a huge dollop on glue on the end of their popsicle stick!91ם King says. 91לThis observation was the start of our investigations of the tip proteins as a collective material.91ם
The MBL awarded King a post-course fellowship so he could follow up on these intriguing results with Dogterom and Reese. The next spring, King spent six weeks in Dogterom's lab in Delft, where they continued the research that would lead to this publication.
Citation:
Renu Maan et al. (2022) Multivalent interactions facilitate motor-dependent protein accumulation at growing microtubule plus-ends. Nature Cell Biology, DOI: