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Annual Review of Biophysics May 2021Dyneins make up a family of AAA+ motors that move toward the minus end of microtubules. Cytoplasmic dynein is responsible for transporting intracellular cargos in... (Review)
Review
Dyneins make up a family of AAA+ motors that move toward the minus end of microtubules. Cytoplasmic dynein is responsible for transporting intracellular cargos in interphase cells and mediating spindle assembly and chromosome positioning during cell division. Other dynein isoforms transport cargos in cilia and power ciliary beating. Dyneins were the least studied of the cytoskeletal motors due to challenges in the reconstitution of active dynein complexes in vitro and the scarcity of high-resolution methods for in-depth structural and biophysical characterization of these motors. These challenges have been recently addressed, and there have been major advances in our understanding of the activation, mechanism, and regulation of dyneins. This review synthesizes the results of structural and biophysical studies for each class of dynein motors. We highlight several outstanding questions about the regulation of bidirectional transport along microtubules and the mechanisms that sustain self-coordinated oscillations within motile cilia.
Topics: Animals; Biological Transport; Cilia; Dyneins; Humans; Intracellular Space; Microtubules
PubMed: 33957056
DOI: 10.1146/annurev-biophys-111020-101511 -
Cold Spring Harbor Perspectives in... Jan 2017The axoneme is the main extracellular part of cilia and flagella in eukaryotes. It consists of a microtubule cytoskeleton, which normally comprises nine doublets. In... (Review)
Review
The axoneme is the main extracellular part of cilia and flagella in eukaryotes. It consists of a microtubule cytoskeleton, which normally comprises nine doublets. In motile cilia, dynein ATPase motor proteins generate sliding motions between adjacent microtubules, which are integrated into a well-orchestrated beating or rotational motion. In primary cilia, there are a number of sensory proteins functioning on membranes surrounding the axoneme. In both cases, as the study of proteomics has elucidated, hundreds of proteins exist in this compartmentalized biomolecular system. In this article, we review the recent progress of structural studies of the axoneme and its components using electron microscopy and X-ray crystallography, mainly focusing on motile cilia. Structural biology presents snapshots (but not live imaging) of dynamic structural change and gives insights into the force generation mechanism of dynein, ciliary bending mechanism, ciliogenesis, and evolution of the axoneme.
Topics: Animals; Axoneme; Chlamydomonas; Cilia; Crystallography, X-Ray; Dyneins; Microscopy, Electron; Proteins
PubMed: 27601632
DOI: 10.1101/cshperspect.a028076 -
Trends in Biochemical Sciences Jan 2016Cytoplasmic dynein, a member of the AAA (ATPases Associated with diverse cellular Activities) family of proteins, drives the processive movement of numerous... (Review)
Review
Cytoplasmic dynein, a member of the AAA (ATPases Associated with diverse cellular Activities) family of proteins, drives the processive movement of numerous intracellular cargos towards the minus end of microtubules. Here, we summarize the structural and motile properties of dynein and highlight features that distinguish this motor from kinesin-1 and myosin V, two well-studied transport motors. Integrating information from recent crystal and cryoelectron microscopy structures, as well as high-resolution single-molecule studies, we also discuss models for how dynein biases its movement in one direction along a microtubule track, and present a movie that illustrates these principles.
Topics: Animals; Dyneins; Humans; Microtubules; Models, Molecular
PubMed: 26678005
DOI: 10.1016/j.tibs.2015.11.004 -
Biopolymers Aug 2016Dyneins are multiprotein complexes that move cargo along microtubules in the minus end direction. The largest individual component of the dynein complex is the heavy... (Review)
Review
Dyneins are multiprotein complexes that move cargo along microtubules in the minus end direction. The largest individual component of the dynein complex is the heavy chain. Its C-terminal 3500 amino-acid residues form the motor domain, which hydrolyses ATP in its ring of AAA+ (ATPases associated with diverse cellular activities) domains to generate the force for movement. The production of force is synchronized with cycles of microtubule binding and release, another important prerequisite for efficient motility along the microtubule. Although the large scale conformational changes that lead to force production and microtubule affinity regulation are well established, it has been largely enigmatic how ATP-hydrolysis in the AAA+ ring causes these rearrangements. The past five years have seen a surge of high resolution information on the dynein motor domain that finally allowed unprecedented insights into this important open question. This review, part of the "ATP and GTP hydrolysis in Biology" special issue, will summarize our current understanding of the dynein motor mechanism with a special emphasis on the recently obtained crystal and EM structures. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 557-567, 2016.
Topics: Adenosine Triphosphate; Animals; Dyneins; Humans; Hydrolysis; Microtubules; Movement; Protein Domains
PubMed: 27062277
DOI: 10.1002/bip.22856 -
Cellular and Molecular Life Sciences :... Sep 2015Microtubule-based distribution of organelles/vesicles is crucial for the function of many types of eukaryotic cells and the molecular motor cytoplasmic dynein is... (Review)
Review
Microtubule-based distribution of organelles/vesicles is crucial for the function of many types of eukaryotic cells and the molecular motor cytoplasmic dynein is required for transporting a variety of cellular cargos toward the microtubule minus ends. Early endosomes represent a major cargo of dynein in filamentous fungi, and dynein regulators such as LIS1 and the dynactin complex are both required for early endosome movement. In fungal hyphae, kinesin-3 and dynein drive bi-directional movements of early endosomes. Dynein accumulates at microtubule plus ends; this accumulation depends on kinesin-1 and dynactin, and it is important for early endosome movements towards the microtubule minus ends. The physical interaction between dynein and early endosome requires the dynactin complex, and in particular, its p25 component. The FTS-Hook-FHIP (FHF) complex links dynein-dynactin to early endosomes, and within the FHF complex, Hook interacts with dynein-dynactin, and Hook-early endosome interaction depends on FHIP and FTS.
Topics: Biological Transport; Cytoplasm; Dyneins; Endosomes; Fungi; Microtubules; Models, Biological
PubMed: 26001903
DOI: 10.1007/s00018-015-1926-y -
Journal of Biomechanical Engineering Feb 2018Motor proteins play critical roles in the normal function of cells and proper development of organisms. Among motor proteins, failings in the normal function of two... (Review)
Review
Motor proteins play critical roles in the normal function of cells and proper development of organisms. Among motor proteins, failings in the normal function of two types of proteins, kinesin and dynein, have been shown to lead many pathologies, including neurodegenerative diseases and cancers. As such, it is critical to researchers to understand the underlying mechanics and behaviors of these proteins, not only to shed light on how failures may lead to disease, but also to guide research toward novel treatment and nano-engineering solutions. To this end, many experimental techniques have been developed to measure the force and motility capabilities of these proteins. This review will (a) discuss such techniques, specifically microscopy, atomic force microscopy (AFM), optical trapping, and magnetic tweezers, and (b) the resulting nanomechanical properties of motor protein functions such as stalling force, velocity, and dependence on adenosine triphosophate (ATP) concentrations will be comparatively discussed. Additionally, this review will highlight the clinical importance of these proteins. Furthermore, as the understanding of the structure and function of motor proteins improves, novel applications are emerging in the field. Specifically, researchers have begun to modify the structure of existing proteins, thereby engineering novel elements to alter and improve native motor protein function, or even allow the motor proteins to perform entirely new tasks as parts of nanomachines. Kinesin and dynein are vital elements for the proper function of cells. While many exciting experiments have shed light on their function, mechanics, and applications, additional research is needed to completely understand their behavior.
Topics: Adenosine Triphosphate; Dyneins; Humans; Kinesins; Mechanical Phenomena; Protein Engineering
PubMed: 28901373
DOI: 10.1115/1.4037886 -
Experimental Cell Research May 2015
Review
Topics: Biological Transport; Dyneins; Flagella; Humans
PubMed: 25725253
DOI: 10.1016/j.yexcr.2015.02.017 -
Cold Spring Harbor Perspectives in... Aug 2017Ciliary motility is crucial for the development and health of many organisms. Motility depends on the coordinated activity of multiple dynein motors arranged in a... (Review)
Review
Ciliary motility is crucial for the development and health of many organisms. Motility depends on the coordinated activity of multiple dynein motors arranged in a precise pattern on the outer doublet microtubules. Although significant progress has been made in elucidating the composition and organization of the dyneins, a comprehensive understanding of dynein regulation is lacking. Here, we focus on two conserved signaling complexes located at the base of the radial spokes. These include the I1/ inner dynein arm associated with radial spoke 1 and the calmodulin- and spoke-associated complex and the nexin-dynein regulatory complex associated with radial spoke 2. Current research is focused on understanding how these two axonemal hubs coordinate and regulate the dynein motors and ciliary motility.
Topics: Animals; Axoneme; Cilia; Dyneins; Humans; Movement
PubMed: 28765157
DOI: 10.1101/cshperspect.a018325 -
Nature Communications Sep 2023Processive transport by the microtubule motor cytoplasmic dynein requires the regulated assembly of a dynein-dynactin-adapter complex. Interactions between dynein and...
Processive transport by the microtubule motor cytoplasmic dynein requires the regulated assembly of a dynein-dynactin-adapter complex. Interactions between dynein and dynactin were initially ascribed to the dynein intermediate chain N-terminus and the dynactin subunit p150. However, recent cryo-EM structures have not resolved this interaction, questioning its importance. The intermediate chain also interacts with Nde1/Ndel1, which compete with p150 for binding. We reveal that the intermediate chain N-terminus is a critical evolutionarily conserved hub that interacts with dynactin and Ndel1, the latter of which recruits LIS1 to drive complex assembly. In additon to revealing that the intermediate chain N-terminus is likely bound to p150 in active transport complexes, our data support a model whereby Ndel1-LIS1 must dissociate prior to LIS1 being handed off to dynein in temporally discrete steps. Our work reveals previously unknown steps in the dynein activation pathway, and provide insight into the integrated activities of LIS1/Ndel1 and dynactin/cargo-adapters.
Topics: Dyneins; Dynactin Complex; Cytoplasmic Dyneins; Actin Cytoskeleton; Cytoskeleton
PubMed: 37730751
DOI: 10.1038/s41467-023-41466-5 -
The Journal of Cell Biology Nov 2005A variety of names has been used in the literature for the subunits of cytoplasmic dynein complexes. Thus, there is a strong need for a more definitive consensus...
A variety of names has been used in the literature for the subunits of cytoplasmic dynein complexes. Thus, there is a strong need for a more definitive consensus statement on nomenclature. This is especially important for mammalian cytoplasmic dyneins, many subunits of which are encoded by multiple genes. We propose names for the mammalian cytoplasmic dynein subunit genes and proteins that reflect the phylogenetic relationships of the genes and the published studies clarifying the functions of the polypeptides. This nomenclature recognizes the two distinct cytoplasmic dynein complexes and has the flexibility to accommodate the discovery of new subunits and isoforms.
Topics: Animals; Cytoplasm; Dyneins; Humans; Terminology as Topic
PubMed: 16260502
DOI: 10.1083/jcb.200508078