Cell and Developmental Biology Programme Roop Mallik

26/09/202511:00R_473.10_AULACell and Developmental Biology ProgrammeRoop MallikIndian Institute of Technology BombayThe Dynein Motor and it's Catch Bond in Intracellular TransportHost: Benito Mestres, MartaAbstract:Molecular Motors generate Force to transport many kinds of vesicles in bidirectional (i.e. back-and-forth) manner along microtubules inside cells. We have used Optical Tweezers to measure these forces and inferred that the transport of Endosomes involves a team of seven to ten Dynein motors that engages in Tug-of-War against one or two Kinesin motors. Given the larger number of dyneins and the known ON/OFF rates for motors, it appears that endosome motion should be dominated by Dynein. So, how does Kinesin ever get a chance to bring about the bidirectional vesicle motion so commonly seen inside cells ?
Biology often shows us examples of a counter-intuitive "Catch-bond" state, where mechanical shear force actually causes Receptor-Ligand interactions to get stronger. We postulate that Tug-of-wars against Kinesin cause Dynein to get catch-bonded to the microtubule, forcing Dyneins into an off-pathway inactive state. Dynein needs time to recover from this inactive state, permitting Kinesin to engage and transport the cargo towards plus direction, thus allowing for the bidirectional transport of endosomes. We present direct evidence for phenomenon in optical trapping data, where we induce a Catch-bond on Dynein using the trap. To the best of our knowledge, the possibility of a post-catch bond inactive state has never been discussed for any Receptor-Ligand interaction interaction in Biology.
Time permitting, we will also discuss Lipid Droplets that are also transported by motors inside your liver. I will discuss how this transport reflects in a blood test, and how we might possibly be able to control it for therapeutic benefits.