Dynein

Dynein
TheTrappist · CC BY-SA 3.0 · source
Name	Dynein
Discovered	1960s
Discoverer	Ian R. Gibbons; Roger W. Sperry
Type	Motor protein
Location	Eukaryota

Dynein Dynein is a large microtubule-based motor protein complex that converts chemical energy into mechanical work to drive directed movement along cytoskeletal tracks. First characterized in the 1960s in studies of cilia and flagella, dynein plays central roles in intracellular transport, mitotic spindle positioning, and axonal trafficking across diverse taxa such as Homo sapiens, Saccharomyces cerevisiae, Chlamydomonas reinhardtii, Drosophila melanogaster, and Caenorhabditis elegans.

Overview

Dynein is a minus-end-directed ATPase that moves toward the microtubule-organizing center in cells such as those studied by groups at Max Planck Society, Cold Spring Harbor Laboratory, Harvard University, University of Cambridge, and Stanford University. Research on dynein intersects work on organelles like mitochondrions examined in laboratories led by investigators affiliated with National Institutes of Health, European Molecular Biology Laboratory, and The Rockefeller University. Early electron microscopy and cryo-EM reconstructions by teams at MRC Laboratory of Molecular Biology and HHMI revealed the complex architecture that underlies its function. Dynein is distinct from kinesin families characterized in studies at California Institute of Technology and University of California, San Francisco.

Structure and Types

Dynein exists in multiple forms including axonemal dyneins first defined in Sven-Tore Jakobsson-era motility studies and cytoplasmic dyneins identified in genetic screens at Columbia University and University of California, Berkeley. The core heavy chain contains an AAA+ ATPase ring motif similar to those described in ATP synthase and ClpX, with linker and stalk domains resolved by cryo-EM from groups at University of Oxford and EMBL. Accessory chains such as intermediate chains and light chains include proteins homologous to those reported by labs at University of Wisconsin–Madison and Johns Hopkins University. Axonemal dyneins form rows on doublet microtubules in structures investigated during the characterization of 9+2 axonemes and nodal cilia in work associated with Yale University and University of Pennsylvania. Cytoplasmic dynein-1 and dynein-2 (also called axonemal IFT dynein) were distinguished in genetic mapping projects at Broad Institute and Sanger Institute.

Mechanism of Motion

Dynein’s motor domain couples ATP hydrolysis to conformational changes in the AAA+ ring and linker to produce a powerstroke analogous to mechanisms studied in Myosin II research at University of Minnesota and rotary catalysis models from University of Geneva. Structural studies by cryo-EM groups at University of Tokyo, MIT, and Weizmann Institute of Science resolved nucleotide-dependent states that coordinate microtubule binding via the stalk and microtubule-binding domain, a theme explored in parallel with kinesin studies from Columbia University. Processivity and stepping behavior were quantified with single-molecule assays developed at Heinrich Pette Institute and University of Illinois Urbana-Champaign, drawing on optical trapping methods pioneered at Bell Labs and Caltech.

Cellular Functions

Dynein drives retrograde axonal transport in neurons investigated in clinics linked to Massachusetts General Hospital and Mayo Clinic, mediates positioning of the mitotic spindle in cell division studies at MIT and Max Planck Institute for Biophysical Chemistry, and powers ciliary beating in developmental contexts probed by researchers at Karolinska Institutet and University of Toronto. It transports cargos including endosomes, lysosomes, and viral particles identified in virology work at NIH and Pasteur Institute, and cooperates with adapter complexes like dynactin characterized by groups at University of California, San Diego and Duke University. Dynein-dependent migrations shape embryogenesis events studied in model organisms such as Xenopus laevis and Zebrafish.

Regulation and Interactions

Dynein activity is regulated by effectors and adaptors including dynactin, LIS1, and Nudel/NudE discovered in genetic and biochemical studies at Scripps Research, University of Chicago, and Rockefeller University. Post-translational modifications such as phosphorylation by kinases studied at Cold Spring Harbor Laboratory and ubiquitination pathways elucidated at European Molecular Biology Laboratory modulate binding to cargo adaptors identified in proteomics efforts at Stanford School of Medicine. Interactions with microtubule-associated proteins like tau and MAP2 were investigated in neurodegeneration studies at University College London and Johns Hopkins University, and coordination with kinesin families during bidirectional transport emerged from collaborative efforts between Harvard Medical School and ETH Zurich.

Medical and Research Relevance

Mutations in dynein and dynein-related genes cause human disorders including spinal muscular atrophy-like syndromes, lissencephaly linked to LIS1 studies, and primary ciliary dyskinesia investigated in clinics at Cleveland Clinic and Great Ormond Street Hospital. Dynein dysfunction is implicated in neurodegenerative diseases researched by groups at Columbia University Irving Medical Center and University of California, San Diego School of Medicine, and in pathogen trafficking pathways explored in publications from Centers for Disease Control and Prevention and Institut Pasteur. Dynein is a target in basic and translational research employing CRISPR screens at Broad Institute, small-molecule modulators studied at pharmaceutical labs including Pfizer and Novartis, and structural drug-discovery pipelines at Genentech and GlaxoSmithKline.

Category:Motor proteins