Journal Article

Autoregulatory mechanism for dynactin control of processive and diffusive dynein transport

Tripathy, Suvranta K., Anand, Preetha, Chen, Chen, Weil, Sarah J., Vallee, Richard B., Gross, Steven P.

2014

Overview

Dynactin is the longest known cytoplasmic dynein regulator, with roles in dynein recruitment to subcellular cargo and in stimulating processive dynein movement. The latter function was thought to involve the N-terminal microtubule-binding region of the major dynactin polypeptide p150 Glued , although recent results disputed this. To understand how dynactin regulates dynein we generated recombinant fragments of the N-terminal half of p150 Glued . We find that the dynein-binding coiled-coil α-helical domain CC1B is sufficient to stimulate dynein processivity, which it accomplishes by increasing average dynein step size and forward-step frequency, while decreasing lateral stepping and microtubule detachment. In contrast, the immediate upstream coiled-coil domain, CC1A, activates a surprising diffusive dynein state. CC1A interacts physically with CC1B and interferes with its effect on dynein processivity. We also identify a role for the N-terminal portion of p150 Glued in coordinating these activities. Our results reveal an unexpected form of long-range allosteric control of dynein motor function by internal p150 Glued sequences, and evidence for p150 Glued autoregulation. Through biochemical and single-molecule analyses, Vallee, Gross and colleagues characterize how subdomains of the dynactin subunit p150 regulate dynein movement along microtubules.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/80/128/1441 / 631/80/128/2343 / Amino Acid Sequence / Animals / Antibodies / Binding Sites / Biology / Cancer Research / Cell Biology / Cellular control mechanisms / Developmental Biology / Dynactin Complex / Dyneins - metabolism / Genetic aspects / Life Sciences / Microtubule-Associated Proteins - genetics / Microtubule-Associated Proteins - metabolism / Microtubules - metabolism / Molecular motors (Biochemistry) / Peptide Fragments - analysis / Peptide Fragments - chemistry / Peptide Fragments - genetics / Polypeptides / Properties / Protein Binding / Protein Structure, Tertiary / Protein Transport / Rats / Recombinant Proteins - genetics / Sf9 Cells / Spodoptera / Stem Cells / Upstream