Cytoplasmic dynein is a multi-protein motor complex responsible for all minus-end directed microtubule transport in most eukaryotic cells. Dynein carries out a large number of functions in the cell and is subject to complicated regulatory control by accessory factors. In relation to the other microtubule motor family, such as kinesins, dynein is much larger and complicated. Despite being identified 20 years earlier than kinesin, dynein’s complexity has made it relatively intractable to study mechanistically until recently. Dynein belongs to the AAA family of ATPases and thus is evolutionarily unrelated to kinesin and myosin.
The Vale lab has a strong interest in the mechanism of dynein motility (see our Review—How Dynein Moves along Microtubules) and how dynein binds indirectly to cargo by way of its adaptor proteins. Our approaches use a combination of tools, including crystallography, cryo-electron microscopy, and single-molecule imaging. In the past, our lab made initial progress in understanding dynein motility by using recombinant yeast dynein as a model, as this was the first dynein that to be recombinantly produced (Reck-Peterson et al 2006). Currently, our work has extended to mammalian dyneins, which have proven to behave quite differently. For example, human cytoplasmic dynein requires a cargo adaptor to move processively along a microtubule (McKenney et al 2014). Recently we made an effort to combine knowledge in the field from different labs to generate a model of how dynein may move along microtubules.
Selected References:
(pdf) – Bhabha, G., Johnson, G.T., Schroeder, C.M., Vale, R.D. (2015) How Dynein Moves Along Microtubules. Trends Biochem. Sci. 41, 94-105
(pdf) –Tanenbaum, M.E., Vale, R.D, and McKenney, R.J. (2013) Cytoplasmic dynein crosslinks and slides anti-parallel microtubules using its two motor domains. eLife 2: 1-20. PMCID: PMC3762337.
(pdf) – McKenney, R.J., Huynh, W., Vale, R.D., Sirajuddin M. (2016) Tyrosination of α-Tubulin Controls The Initiation of Processive Dynein-Dynactin Motility. EMBO J. 35(6): 555-698. PMID:26968983. bioRxiv.
(pdf) –McKenney, R.J., Huynh, W., Tanenbaum, M.E., Bhabha, G. and Vale, R.D. (2014) Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes. Science 345: 337-341. NIHMS639978. PMCID: PMC4224444.
(pdf) – Schroeder, C.M., Ostrem, J.M.L., Hertz, N.T. and Vale, R.D. (2014) A Ras-like domain in the light intermediate chain bridges the dynein motor to a cargo-binding region. eLife 3: e03351. PMCID: PMC4359372.
(pdf) –Bhabha, G., Cheng, H.C., Zhang, N., Moeller, A., Liao, M., Speir, J.A., Cheng, Y., and Vale, R.D. (2014) Allosteric communication in the Dynein motor domain. Cell 159: 857-868. PMCID: PMC4269335