Lis1 activates dynein motility by pairing it with dynactin
ElShenawy, M.; Kusakci, E.; Volz, S.; Baumbach, J.; Bullock, S. L.; Yildiz, A.
Show abstract
Lissencephaly-1 (Lis1) is a key cofactor for dynein-mediated intracellular transport towards the minus-ends of microtubules (MTs). It remains unclear whether Lis1 serves as an inhibitor or an activator of mammalian dynein motility. Here we use single-molecule imaging and optical trapping to show that Lis1 does not directly alter the stepping and force production of individual dynein motors assembled with dynactin and a cargo adaptor. Instead, Lis1 binding releases dynein from its auto-inhibited state and thereby promotes the formation of an active complex with dynactin. Lis1 also favors recruitment of two dyneins to dynactin, resulting in increased velocity, higher force production and more effective competition against kinesin in a tug-of-war. Lis1 dissociates from motile complexes, indicating that its primary role is to orchestrate the assembly of the transport machinery. These results provide a mechanistic explanation for why Lis1 is required for efficient transport of many dynein-associated cargoes in cells.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments 97%
- A protein complex in the extreme distal tip of vertebrate motilecilia controls their organization, length, and function 96%
- Control of Motor Landing and Processivity by the CAP-Gly Domain in the KIF13B Tail 96%
Similar papers in this journal
- The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor 97%
- Hundreds of myosin 10s are pushed to the tips of filopodia and could cause traffic jams on actin 95%
- The transition state and regulation of γ-TuRC-mediated microtubule nucleation revealed by single molecule microscopy 95%
Similar papers in this journal
- Three-color single-molecule imaging reveals conformational dynamics of dynein undergoing motility 97%
- A noncanonical GTPase signaling mechanism controls exit from mitosis in budding yeast 96%
- Nucleation of the destruction complex on the centrosome accelerates degradation of β-catenin and regulates Wnt signal transmission 95%
Similar papers in this journal
- HIV-1 binds dynein directly to hijack microtubule transport machinery 96%
- A tonically active master neuron continuously modulates mutually exclusive motor states at two timescales 96%
- Afadin mediates cadherin-catenin complex clustering on F-actin linked to cooperative binding and filament curvature 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.