dynein

ダイニン

WordNet

1. a unit of force equal to the force that imparts an acceleration of 1 cm/sec/sec to a mass of 1 gram

PrepTutorEJDIC

1. ダイン(力の絶対単位;1グラムの物体に1秒につき1cm/秒の加速度を生じる力)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/06/15 22:38:08」(JST)

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Cytoplasmic dynein on a microtubule

Cytoplasmic dynein has two heavy chains with globular "heads" that "walk" along the microtubule, to which they are bound by the "stalks". Dynactin (not shown) may help attach the light chains to the cargo. Interactions between the "stalks" and the microtubule must repeatedly form and break (see main text for details)

Dynein is a family of cytoskeletal motor proteins that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargos, provides forces and displacements important in mitosis, and drives the beat of eukaryotic cilia and flagella. All of these functions rely on dynein's ability to move towards the minus-end of the microtubules, known as retrograde transport, thus, they are called "minus-end directed motors." In contrast, kinesin motor proteins move toward the microtubules' plus end.

Classification

Dynein heavy chain, N-terminal region 1
Identifiers
Symbol	DHC_N1
Pfam	PF08385
InterPro	IPR013594
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Dynein heavy chain, N-terminal region 2
Identifiers
Symbol	DHC_N2
Pfam	PF08393
InterPro	IPR013602
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Dynein heavy chain and region D6 of dynein motor
Identifiers
Symbol	Dynein_heavy
Pfam	PF03028
InterPro	IPR004273
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Dynein light intermediate chain (DLIC)
Identifiers
Symbol	DLIC
Pfam	PF05783
Pfam clan	CL0023
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Dynein light chain type 1
structure of the human pin/lc8 dimer with a bound peptide
Identifiers
Symbol	Dynein_light
Pfam	PF01221
InterPro	IPR001372
PROSITE	PDOC00953
SCOP	1bkq
SUPERFAMILY	1bkq
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Dyneins can be divided into two groups: cytoplasmic dyneins and axonemal dyneins, which are also called ciliary or flagellar dyneins.

• axonemal
  • heavy chain: DNAH1, DNAH2, DNAH3, DNAH5, DNAH6, DNAH7, DNAH8, DNAH9, DNAH10, DNAH11, DNAH12, DNAH13, DNAH14, DNAH17
  • intermediate chain: DNAI1, DNAI2
  • light intermediate chain: DNALI1
  • light chain: DNAL1, DNAL4
• cytoplasmic
  • heavy chain: DYNC1H1, DYNC2H1
  • intermediate chain: DYNC1I1, DYNC1I2
  • light intermediate chain: DYNC1LI1, DYNC1LI2, DYNC2LI1
  • light chain: DYNLL1, DYNLL2, DYNLRB1, DYNLRB2, DYNLT1, DYNLT3

Function

Axonemal dynein causes sliding of microtubules in the axonemes of cilia and flagella and is found only in cells that have those structures.

Cytoplasmic dynein, found in all animal cells and possibly plant cells as well, performs functions necessary for cell survival such as organelle transport and centrosome assembly. Cytoplasmic dynein moves processively along the microtubule; that is, one or the other of its stalks is always attached to the microtubule so that the dynein can "walk" a considerable distance along a microtubule without detaching.

Cytoplasmic dynein helps to position the Golgi complex and other organelles in the cell. It also helps transport cargo needed for cell function such as vesicles made by the endoplasmic reticulum, endosomes, and lysosomes (Karp, 2005). Dynein is involved in the movement of chromosomes and positioning the mitotic spindles for cell division. Dynein carries organelles, vesicles and possibly microtubule fragments along the axons of neurons toward the cell body in a process called retrograde axoplasmic transport.

Mitotic Spindle Positioning

Cytoplasmic dynein positions the spindle at the site of cytokinesis by anchoring to the cell cortex and pulling on astral microtubules emanating from centrosome. Budding yeast have been a powerful model organism to study this process and has shown that dynein is targeted to plus ends of astral microtubules and delivered to the cell cortex via an offloading mechanism.

Structure

Each molecule of the dynein motor is a complex protein assembly composed of many smaller polypeptide subunits. Cytoplasmic and axonemal dynein contain some of the same components, but they also contain some unique subunits.

Human Cytoplasmic Dynein 2 Domains. Shown is the order of regions of interest for human cytoplasmic dynein 2 motor domains as they occur from the Linker to C-terminal. This is oriented to demonstrate the general bound position on Dynein on a microtubule. The Mirror effect allows the view to observe the Dynein from both sides of the complex.

Cytoplasmic dynein

Cytoplasmic dynein, which has a molecular mass of about 1.5 megadaltons (MDa), is a dimer of dimers, containing approximately twelve polypeptide subunits: two identical "heavy chains", 520 kDa in mass, which contain the ATPase activity and are thus responsible for generating movement along the microtubule; two 74 kDa intermediate chains which are believed to anchor the dynein to its cargo; two 53–59 kDa light intermediate chains; and several light chains..

The force-generating ATPase activity of each dynein heavy chain is located in its large doughnut-shaped "head", which is related to other AAA proteins, while two projections from the head connect it to other cytoplasmic structures. One projection, the coiled-coil stalk, binds to and "walks" along the surface of the microtubule via a repeated cycle of detachment and reattachment. The other projection, the extended tail, binds to the light intermediate, intermediate and light chain subunits which attach dynein to its cargo. The alternating activity of the paired heavy chains in the complete cytoplasmic dynein motor enables a single dynein molecule to transport its cargo by "walking" a considerable distance along a microtubule without becoming completely detached.

Yeast dynein can walk along microtubules without detaching, however in metazoans, cytoplasmic dynein must be activated by the binding of dynactin, another multisubunit protein that is essential for mitosis, and a cargo adaptor. The tri-complex, which includes dynein, dynactin and a cargo adaptor, is ultra-processive and can walk long distances without detaching in order to reach the cargo's intracellular destination. Cargo adaptors identified thus far include BicD2, Hook3, FIP3 and Spindly. The light intermediate chain, which is a member of the Ras superfamily, mediates the attachment of several cargo adaptors to the dynein motor. The other tail subunits may also help facilitate this interaction as evidenced in a low resolution structure of dynein-dynactin-BicD2.

One major form of motor regulation within cells for dynein is dynactin. It may be required for almost all cytoplasmic dynein functions. Currently, it is the best studied dynein partner. Dynactin is a protein that aids in intracellular transport throughout the cell by linking to cytoplasmic dynein. Dynactin can function as a scaffold for other proteins to bind to. It also functions as a recruiting factor that localizes dynein to where it should be. There is also some evidence suggesting that it may regulate kinesin-2. The dynactin complex is composed of more than 20 subunits, of which p150(Glued) is the largest. There is no definitive evidence that dynactin by itself affects the velocity of the motor. It does, however, affect the processivity of the motor. The binding regulation is likely allosteric: experiments have shown that the enhancements provided in the processivity of the dynein motor do not depend on the p150 subunit binding domain to the microtubules.

Axonemal dynein

A cross-section of an axoneme, with axonemal dynein arms

Axonemal dyneins come in multiple forms that contain either one, two or three non-identical heavy chains (depending upon the organism and location in the cilium). Each heavy chain has a globular motor domain with a doughnut-shaped structure believed to resemble that of other AAA proteins, a coiled coil "stalk" that binds to the microtubule, and an extended tail (or "stem") that attaches to a neighboring microtubule of the same axoneme. Each dynein molecule thus forms a cross-bridge between two adjacent microtubules of the ciliary axoneme. During the "power stroke", which causes movement, the AAA ATPase motor domain undergoes a conformational change that causes the microtubule-binding stalk to pivot relative to the cargo-binding tail with the result that one microtubule slides relative to the other (Karp, 2005). This sliding produces the bending movement needed for cilia to beat and propel the cell or other particles. Groups of dynein molecules responsible for movement in opposite directions are probably activated and inactivated in a coordinated fashion so that the cilia or flagella can move back and forth. The radial spoke has been proposed as the (or one of the) structures that synchronizes this movement.

The regulation of axonemal dynein activity is critical for flagellar beat frequency and cilia waveform. Modes of axonemal dynein regulation include phosphorylation, redox, and calcium. Mechanical forces on the axoneme also affect anoxemal dynein function. The heavy chains of inner and outer arms of axonemal dynein are phosphorylated/dephosphorylated to control the rate of microtubule sliding. Thioredoxins associated with the other axonemal dynein arms are oxidized/reduced to regulate where dynein binds in the axoneme. Centerin and components of the outer axonemal dynein arms detect fluctuations in calcium concentration. Calcium fluctuations play an important role in altering cilia waveform and flagellar beat frequency (King, 2012).

History

The protein responsible for movement of cilia and flagella was first discovered and named dynein in 1963 (Karp, 2005). 20 years later, cytoplasmic dynein, which had been suspected to exist since the discovery of flagellar dynein, was isolated and identified (Karp, 2005).

Chromosome segregation during meiosis

Segregation of homologous chromosomes to opposite poles of the cell occurs during the first division of meiosis. Proper segregation is essential for producing haploid meiotic products with a normal complement of chromosomes. The formation of chiasmata (crossover recombination events) appears to generally facilitate proper segregation. However, in the fission yeast Schizosaccharomyces pombe, when chiasmata are absent, dynein promotes segregation. Dhc1, the motor subunit of dynein, is required for chromosomal segregation in both the presence and absence of chiasmata. The dynein light chain Dlc1 protein is also required for segregation, specifically when chiasmata are absent.

See also

• Molecular motors

Further reading

• Karp G (2005). Cell and Molecular Biology: Concepts and Experiments (4th ed.). Hoboken, NJ: John Wiley and Sons. pp. 346–358. ISBN 0-471-19279-1. 
• Schroer TA (2004). "Dynactin". Annual Review of Cell and Developmental Biology. 20: 759–79. PMID 15473859. doi:10.1146/annurev.cellbio.20.012103.094623. 

External links

• Eukaryotic Linear Motif resource motif class LIG_Dynein_DLC8_1
• The Dynein Homepage
• Ron Vale's seminar: Cytoskeletal Motor Proteins
• Dynein at the US National Library of Medicine Medical Subject Headings (MeSH)
• EC 3.6.4.2

UpToDate Contents

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English Journal

• Tianeptine interferes with microtubule organization and hormone secretion of pheochromocytoma cells.

• Makani V, Hall J, Qamar K, Jain P, Jang Y, Hensley K, Park JJ.SourceDepartment of Neurosciences, University of Toledo, College of Medicine and Life Science, Toledo, OH 43614, United States.
• Molecular and cellular endocrinology.Mol Cell Endocrinol.2013 Dec 5;381(1-2):175-87. doi: 10.1016/j.mce.2013.07.033. Epub 2013 Aug 7.
• Pheochromocytoma originates from chromaffin cells in the adrenal medulla and sympathetic paraganglia. 36-53% of pheochromocytoma becomes malignant and, thereafter, resistant to conventional treatments. Pheochromocytoma also causes hyper-secretion of catecholamines that cause severe hypertension. We
• PMID 23933152

• LIS1 functions in normal development and disease.

• Reiner O, Sapir T.SourceDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: orly.reiner@weizmann.ac.il.
• Current opinion in neurobiology.Curr Opin Neurobiol.2013 Dec;23(6):951-6. doi: 10.1016/j.conb.2013.08.001. Epub 2013 Aug 23.
• LIS1, the first gene to be identified as involved in a neuronal migration disease, is a dosage-sensitive gene whose proper levels are required for multiple aspects of cortical development. Deletions in LIS1 result in a severe brain malformation, known as lissencephaly, whereas duplications delay bra
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Japanese Journal

• ゾウリムシを用いた研究から明らかになった繊毛のエネルギー供給と運動調節機構

• 久冨 理,堀 学
• 原生動物学雑誌 47(1・2), 13-27, 2014-10
• NAID 40020272392

• Functional Diversity of Axonemal Dyneins As Assessed by In Vitro and In Vivo Motility Assays of Chlamydomonas Mutants

• Kamiya Ritsu,Yagi Toshiki
• Zoological science 31(10), 633-644, 2014-10
• NAID 40020231543

• 頭足類生殖システムにおける代替的適応形質の制御基盤 : 総合的オーム解析

• 広橋 教貴
• 島根大学生物資源科学部研究報告 19, 9-12, 2014-09-30
• … A family encoding dynein heavy chain gene, however, was found to be biased towards sneakers, whereas many enzymes involving energy metabolism were heavily biased towards consort spermatozoa. …
• NAID 110009831948

Related Links

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• Dynein 2013 International Workshop

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