Activation and Regulation of Cytoplasmic Dynein.

Trends Biochem Sci

Biophysics Graduate Group, University of California at Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cellular Biology, University of California at Berkeley, Berkeley, CA 94720, USA; Physics Department, University of California at Berkeley, Berkeley, CA 94720, USA. Electronic address:

Published: May 2020

Cytoplasmic dynein is an AAA motor that drives the transport of many intracellular cargoes towards the minus end of microtubules (MTs). Previous in vitro studies characterized isolated dynein as an exceptionally weak motor that moves slowly and diffuses on an MT. Recent studies altered this view by demonstrating that dynein remains in an autoinhibited conformation on its own, and processive motility is activated when it forms a ternary complex with dynactin and a cargo adaptor. This complex assembles more efficiently in the presence of Lis1, providing an explanation for why Lis1 is a required cofactor for most cytoplasmic dynein-driven processes in cells. This review describes how dynein motility is activated and regulated by cargo adaptors and accessory proteins.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179903PMC
http://dx.doi.org/10.1016/j.tibs.2020.02.002DOI Listing

Publication Analysis

Top Keywords

cytoplasmic dynein
8
motility activated
8
dynein
5
activation regulation
4
regulation cytoplasmic
4
dynein cytoplasmic
4
dynein aaa
4
aaa motor
4
motor drives
4
drives transport
4

Similar Publications

Dynein-1 is a microtubule motor responsible for the transport of cytoplasmic cargoes. Activation of motility requires it first overcome an autoinhibited state prior to its assembly with dynactin and a cargo adaptor. Studies suggest that Lis1 may relieve dynein's autoinhibited state.

View Article and Find Full Text PDF

Nde1 Promotes Lis1 Binding to Full-Length Autoinhibited Human Dynein-1.

bioRxiv

December 2024

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06511, USA.

Cytoplasmic dynein-1 (dynein) is the primary motor for the retrograde transport of intracellular cargoes along microtubules. The activation of the dynein transport machinery requires the opening of its autoinhibited Phi conformation by Lis1 and Nde1/Ndel1, but the underlying mechanism remains unclear. Using biochemical reconstitution and cryo-electron microscopy, we show that Nde1 significantly enhances Lis1 binding to autoinhibited dynein and facilitates the opening of Phi.

View Article and Find Full Text PDF

Molecular basis for the assembly of the dynein transport machinery on microtubules.

bioRxiv

December 2024

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06511, USA.

Cytoplasmic dynein-1, a microtubule-based motor protein, requires dynactin and an adaptor to form the processive dynein-dynactin-adaptor (DDA) complex. The role of microtubules in DDA assembly has been elusive. Here, we reveal detailed structural insights into microtubule-mediated DDA assembly using cryo-electron microscopy.

View Article and Find Full Text PDF

Dyneins are huge motor protein complexes that are essential for cell motility, cell division, and intracellular transport. Dyneins are classified into three major subfamilies, namely cytoplasmic, intraflagellar-transport (IFT), and ciliary dyneins, based on their intracellular localization and functions. Recently, several near-atomic resolution structures have been reported for cytoplasmic/IFT dyneins.

View Article and Find Full Text PDF

The microtubule motor cytoplasmic dynein-1 transports and positions various organelles, but the molecular basis of this functional diversity is not fully understood. Cargo adaptors of the Hook protein family recruit dynein to early endosomes (EE) in fungi and human cells by forming the FTS-Hook-FHIP (FHF) complex. By contrast, the Hook homolog ZYG-12 recruits dynein to the nuclear envelope (NE) in the meiotic gonad and mitotic early embryo by forming a Linker of Nucleoskeleton and Cytoskeleton (LINC) complex.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!