DCTN6

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In molecular biology, DCTN6 is that subunit of the dynactin protein complex that is encoded by the p27 gene. Dynactin is the essential component for microtubule-based cytoplasmic dynein motor activity in intracellular transport of a variety of cargoes and organelles.

Dynactin

Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1).

Microtubule any of the long, generally straight, hollow tubes of internal diameter 12-15 nm and external diameter 24 nm found in a wide variety of eukaryotic cells; each consists (usually) of 13 protofilaments of polymeric tubulin.

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to the cytoplasm of eukaryotic cells, some bacteria and some archaea. A microtubule can grow as long as 50 micrometres and are highly dynamic. The outer diameter of a microtubule is about 24 nm while the inner diameter is about 12 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

Dynein

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.

Contents

Identification and structure

DCTN6 was first identified and cloned as a subunit of the "pointed-end complex" of dynactin through biochemical purification. [1]

X-ray crystal structure revealed that dynactin p27 forms an unusual left handed β-helix (LβH) domain, and its phosphorylation site T186 is in C-terminal disordered segment. [2]

Function

In intracellular transport

Dynactin p27 forms a hetero-dimer with the other dynactin pointed-end complex subunit p25/DCTN5 in 1:1 ratio, and it is essential for p25 stability since they are co-knockdown by p27 RNAi. However, both p27 and p25 are not required for 19S dynactin complex integrity verified by velocity sedimentation. [3] [4] p27/DCTN6 and other dynactin pointed-end complex subunits (Arp11/Actr10, p62/DCTN4, and p25/DCTN5) have been suggested to be involved in dynactin binding to specific intracellular cargoes. [5] Co-depletion of dynactin p27 and p25 by p27 RNAi affects dynactin binding to endomembrane, and early and recycling endosome movements are impaired, suggesting that p27/p25 form a selective endomembrane cargo-targeting module. [6]

DCTN4 protein-coding gene in the species Homo sapiens

Dynactin subunit 4 is a protein that in humans is encoded by the DCTN4 gene.

DCTN5 protein-coding gene in the species Homo sapiens

Dynactin 5 (p25) is a protein that in humans is encoded by the DCTN5 gene.

Endosome A vacuole to which materials ingested by endocytosis are delivered.

In cell biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway originating from the trans Golgi membrane. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane. Molecules are also transported to endosomes from the trans-Golgi network and either continue to lysosomes or recycle back to the Golgi. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. In HeLa cells, endosomes are approximately 500 nm in diameter when fully mature.

In mitosis

In mitosis, unlike dynactin or dynein perturbation that causes mitotic spindle disarrangement and mitotic arrest, dynactin p27/p25 depletion does not affect mitotic spindle formation, pole focusing or dynein/dynactin targeting to kinetochores. However, dynactin p27/p25 are required for normal chromosome alignment, kinetochore-microtubule interaction, and proper timing of anaphase onset. Dynactin p27 C-terminal T186 residue is phosphorylated by cyclin-dependent kinase 1 (Cdk1) in mitosis and helps target polo-like kinase 1 (Plk1) to kinetochores during prometaphase. This activity facilitates phosphorylation of important downstream kinetochore targets (such as tension-sensing 3F3/2 phospho-epitope) of Plk1, which is important for recruitment of spindle assembly checkpoint proteins such as Mad1 and proper kinetochore-microtubule attachment.

Mitosis nuclear division cycle for eukaryotic cells in which the two resulting nuclei are genetically identical

In cell biology, mitosis is a part of the cell cycle when replicated chromosomes are separated into two new nuclei. Cell division gives rise to genetically identical cells in which the number of chromosomes is maintained. In general, mitosis is preceded by the S stage of interphase and is often accompanied or followed by cytokinesis, which divides the cytoplasm, organelles and cell membrane into two new cells containing roughly equal shares of these cellular components. Mitosis and cytokinesis together define the mitotic (M) phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.

Kinetochore A multisubunit complex that is located at the centromeric region of DNA and provides an attachment point for the spindle microtubules.

A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. Its proteins also help to hold the sister chromatids together and play a role in chromosome editing. In some areas in Asia however, the word is pronounced "connect-a-core", as it connects to the core of the chromosome. Details of the specific areas of origin are unknown.

Chromosome DNA molecule containing genetic material of a cell

A chromosome is a deoxyribonucleic acid (DNA) molecule with part or all of the genetic material (genome) of an organism. Most eukaryotic chromosomes include packaging proteins which, aided by chaperone proteins, bind to and condense the DNA molecule to prevent it from becoming an unmanageable tangle.

Related Research Articles

Spindle apparatus the array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during mitosis or meiosis and serves to move the duplicated chromosomes apart.

In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

During the process of cell division, the spindle checkpoint prevents separation of the duplicated chromosomes until each chromosome is properly attached to the spindle apparatus. In order to preserve the cell's identity and proper function, it is necessary to maintain the appropriate number of chromosomes after each cell division. An error in generating daughter cells with fewer or greater number of chromosomes than expected, may lead in best case to cell death, or alternatively it may generate catastrophic phenotypic results. Examples include:

Aurora B kinase protein-coding gene in the species Homo sapiens

Aurora B kinase is a protein that functions in the attachment of the mitotic spindle to the centromere.

DCTN1 protein-coding gene in the species Homo sapiens

Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.

NDC80 protein-coding gene in the species Homo sapiens

Kinetochore protein NDC80 homolog is a protein that in humans is encoded by the NDC80 gene.

CLIP1 protein-coding gene in the species Homo sapiens

CAP-GLY domain containing linker protein 1, also known as CLIP1, is a protein which in humans is encoded by the CLIP1 gene.

DCTN2 gene of the species Homo sapiens

Dynactin subunit 2 is a protein that in humans is encoded by the DCTN2 gene

MAPRE1 protein-coding gene in the species Homo sapiens

Microtubule-associated protein RP/EB family member 1 is a protein that in humans is encoded by the MAPRE1 gene.

ACTR1A protein-coding gene in the species Homo sapiens

Alpha-centractin (yeast) or ARP1 is a protein that in humans is encoded by the ACTR1A gene.

DYNC1H1 protein-coding gene in the species Homo sapiens

Cytoplasmic dynein 1 heavy chain 1 is a protein that in humans is encoded by the DYNC1H1 gene.

ZW10 protein-coding gene in the species Homo sapiens

Centromere/kinetochore protein zw10 homolog is a protein that in humans is encoded by the ZW10 gene. This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. The encoded protein binds to centromeres during the prophase, metaphase, and early anaphase cell division stages and to kinetochore microtubules during metaphase.

DCTN3 protein-coding gene in the species Homo sapiens

Dynactin subunit 3 is a protein that in humans is encoded by the DCTN3 gene.

ACTR1B protein-coding gene in the species Homo sapiens

Beta-centractin is a protein that in humans is encoded by the ACTR1B gene.

Andrew P. Carter

Andrew P. Carter is a British structural biologist who works at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) in Cambridge, UK. He is known for his work on the microtubule motor dynein.

References

  1. ↑ Eckley, DM; Gill, SR; Melkonian, KA; Bingham, JB; Goodson, HV; Heuser, JE; Schroer, TA (Oct 18, 1999). "Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end". The Journal of Cell Biology. 147 (2): 307–20. doi:10.1083/jcb.147.2.307. PMC   2174220  Lock-green.svg. PMID   10525537.
  2. ↑ Yeh, TY; Kowalska, AK; Scipioni, BR; Cheong, FK; Zheng, M; Derewenda, U; Derewenda, ZS; Schroer, TA (Apr 3, 2013). "Dynactin helps target Polo-like kinase 1 to kinetochores via its left-handed beta-helical p27 subunit". The EMBO Journal. 32 (7): 1023–35. doi:10.1038/emboj.2013.30. PMC   3616283  Lock-green.svg. PMID   23455152.
  3. ↑ Eckley, DM; Gill, SR; Melkonian, KA; Bingham, JB; Goodson, HV; Heuser, JE; Schroer, TA (Oct 18, 1999). "Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end". The Journal of Cell Biology. 147 (2): 307–20. doi:10.1083/jcb.147.2.307. PMC   2174220  Lock-green.svg. PMID   10525537.
  4. ↑ Yeh, TY; Quintyne, NJ; Scipioni, BR; Eckley, DM; Schroer, TA (October 2012). "Dynactin's pointed-end complex is a cargo-targeting module". Molecular Biology of the Cell. 23 (19): 3827–37. doi:10.1091/mbc.E12-07-0496. PMC   3459859  Lock-green.svg. PMID   22918948.
  5. ↑ Schroer, TA (2004). "Dynactin". Annual Review of Cell and Developmental Biology. 20: 759–79. doi:10.1146/annurev.cellbio.20.012103.094623. PMID   15473859.
  6. ↑ Yeh, TY; Quintyne, NJ; Scipioni, BR; Eckley, DM; Schroer, TA (October 2012). "Dynactin's pointed-end complex is a cargo-targeting module". Molecular Biology of the Cell. 23 (19): 3827–37. doi:10.1091/mbc.E12-07-0496. PMC   3459859  Lock-green.svg. PMID   22918948.
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