Name: microtubule growth and shrinkage
Uploaded: 2021-04-07T12:12:01.000Z
Duration: 2 min 17 s
Channel: JoVE

진핵 세포에서 세포 분열 중에 미세소관은 유사 분열 방추체의 주요 구성 요소를 형성하며 염색체 분리에 필요합니다.
미세소관은 매우 역동적입니다. 개별 미세소관은 성장하고 수축하며 성장기와 단축 단계 사이를 빠르게 번갈아 가며 진행됩니다. 미세소관은 성장과 수축 사이의 예측할 수 없는 변화인 동적 불안정성을 나타냅니다.
성장에서 수축으로의 전환을 재앙이라고 하고 수축에서 성장으로의 전환을 구조라고 합니다. 어느 시점에서든 미세소관 그룹은 활발하게 조립되고 있는 반면 다른 그룹은 빠르게 분해되고 있습니다.
미세소관은 GTP 결합 튜불린 이종이량체의 종단 간 중합에 의해 핵을 형성하고 성장합니다. 튜불린 이종이량체는 알파 및 베타 소단위체로 구성됩니다.
베타-튜불린 소단위체는 가수분해 가능한 형태의 GTP에 결합되어 있습니다. GTP에서 GDP로의 가수분해는 미세소관 골격을 불안정하게 만듭니다. 구조는 끝에서 펼쳐지고 효과는 아래로 전파되어 미세소관의 해중합을 유발합니다.
다양한 조절 단백질이 미세소관 역학을 제어합니다. 여러 미세소관 관련 단백질 또는 MAP은 미세소관의 안정성을 촉진하는 반면, 재앙 요인(catastrophe factor)인 다른 여러 단백질은 미세소관을 불안정하게 만듭니다. 세포는 세포주기의 단계에 따라 미세소관 역학을 변화시키기 위해 조절 단백질의 활성을 변경합니다.
예를 들어, 간기(interphase) 동안 대부분의 동물 세포는 단일 중심체에서 방사되는 긴 미세소관의 세포질 배열을 포함합니다. 세포가 유사분열기(mitotic phase)로 전환하고 복제된 중심체가 반대쪽 극으로 이동함에 따라 미세소관 불안정성이 증가합니다.
미세소관의 불안정성은 유사분열 미세소관의 조밀하고 역동적인 배열의 형성을 촉진하여 방추체 형성에 기여합니다.

<ol>
	<li>de Forges, H., Bouissou, A. 및 Perez, F., 2012. 미세소관 역학과 세포 내 조직 간의 상호 작용. 국제생화학 및 세포생물학저널, 44(2), pp.266-274. https://doi.org/10.1016/j.biocel.2011.11.009</li>
	<li>Burbank, KS 및 Mitchison, TJ, 2006. 미세소관 동적 불안정성. Current Biology, 14(16), pp. R516-R517. https://doi.org/10.1016/j.cub.2006.06.044</li>
	<li>Vaart, BVD, Akhmanova, A. 및 Straube, A., 2009. 미세소관 동적 불안정성의 조절. 생화학회논문집, 37(5), pp.1007-1013. https://doi.org/10.1042/BST0371007</li>
</ol>

미세소관 불안정성

Microtubule Instability

미세소관은 직경이 약 25nm이고 길이가 200nm에서 25μm까지 다양한 속이 빈 원통형 섬유입니다. GTP 결합 튜불린 소단위는 미세소관 조립을 위한 αβ-이종이합체를 형성합니다. 이러한 핵심 빌딩 블록은 세로 방향으로 상호 작용하여 프로토섬유로 중합됩니다. 그런 다음 원형섬유는 측면 결합력을 통해 서로 상호 작용하여 안정적인 원통형 미세소관을 형성합니다. 이러한 원통형 섬유는 조립과 분해가 반복되면서 역동적입니다. 이러한 특징적인 동적 불안정성은 생체 내 및 시험관 내에서 모두 발견될 수 있습니다.

동적 불안정성

개별 미세소관은 특정 시점에 반대쪽 끝에서 동시에 늘어나거나 줄어들 수 있습니다. 미세소관이 성장하는지 수축하는지 여부는 재앙과 구조의 속도에 따라 결정됩니다. 재앙은 성장하는 미세소관이 급속히 짧아지기 시작하는 경우입니다. 구조는 수축하는 미세소관을 빠르게 늘리는 것입니다. β-튜불린 결합-GTP 가수분해 속도는 동적 불안정성을 결정하는 주요 요인입니다.

세포에서는 유리 튜불린 소단위와 αβ-이종이합체 형태가 모두 세포질 풀에 존재합니다. 튜불린 소단위의 중합은 GTP 결합 αβ-이종이량체 소단위가 미세소관 중합을 위한 임계 농도라고 불리는 임계 농도 이상일 때 시작됩니다. β-튜불린은 두 가지 형태로 존재합니다. GTP 결합 β-튜불린 또는 T형은 미세소관의 신장과 안정적인 선형 구조를 담당합니다. 대조적으로, GDP-결합된 β-튜불린 또는 D-형태는 미세소관 분해를 선호합니다. 성장 말단의 GTP 결합 베타튜불린은 캡 역할을 하여 원형섬유 곡률을 방지하고 신장을 촉진합니다. GTP가 가수분해되면 β-튜불린의 형태가 약간 변경되어 원형섬유가 휘어집니다. 이러한 곡선화는 stathmin 및 kinesin-13과 같은 불안정화 단백질의 결합을 촉진하여 αβ-튜불린 이종이량체를 제거합니다.

불안정성을 조절하는 요인

미세소관 관련 단백질 또는 MAP는 미세소관 동적 불안정성의 중요한 조절자입니다. MAP는 미세소관 역학에서의 기능에 따라 안정제와 불안정제로 광범위하게 분류됩니다. 안정화제 MAP는 미세소관과 결합하여 재앙을 줄이고 신장을 촉진합니다. 반면에 불안정화 요인은 재앙을 촉진하기 위해 결합합니다. 안정제 MAP는 간기와 뉴런의 축삭 및 수지상 미세소관에서 지배적이며 안정적인 어셈블리를 촉진합니다. 유사분열 중에는 불안정화 MAP가 더 일반적입니다. 이러한 MAP는 염색체 분리와 세포 분열을 위한 세포골격 메시의 분해를 담당합니다.

미세소관은 직경이 약 25nm이고 길이가 200nm에서 25μm까지 다양한 중공 원통형 필라멘트입니다. GTP 결합 ...

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 2

제2단원

Cell Division

세포 분열

KEY TERMS AND CONCEPTS

주요 용어 및 개념

microtubule growth and shrinkage

Microtubules are hollow, cylindrical filaments in the cell. They are about 25 nm wide and can range from 200 nm to 25 μm in length. Their main building blocks are GTP-bound tubulin subunits that form αβ-heterodimers, which then assemble into protofilaments. These protofilaments join by lateral bonds to create stable microtubule cylinders.

Microtubules are highly dynamic because they repeatedly assemble and break down. They can even grow on one end while shrinking on the other at the same time. This behavior is called dynamic instability. It is seen both in living cells and in vitro.

Whether a microtubule grows or shortens depends on catastrophe and rescue. Catastrophe is the rapid switch from growth to shrinkage. Rescue is the switch from shrinkage back to growth. The rate of GTP hydrolysis on β-tubulin is a major factor that controls this behavior.

Cells contain both free tubulin subunits and αβ-heterodimers in the cytoplasmic pool. Polymerization starts when GTP-bound αβ-heterodimers rise above the critical concentration for microtubule polymerization. β-tubulin also exists in two forms. The GTP-bound T-form supports elongation and a stable, straight microtubule. The GDP-bound D-form favors disassembly.

At the growing end, GTP-bound β-tubulin forms a cap that helps block protofilament bending and supports elongation. When GTP is hydrolyzed, β-tubulin changes shape slightly and protofilaments curve. This curved state helps destabilizing proteins such as stathmin and kinesin-13 bind and remove αβ-tubulin heterodimers.

Microtubule-associated proteins, or MAPs, also regulate dynamic instability. Some MAPs stabilize microtubules, while others promote destabilization. Stabilizer MAPs reduce catastrophe and support elongation. They are common during interphase and in the axonal and dendritic microtubules of neurons, where stable structures are needed. During mitosis, destabilizer MAPs are more common. They help chromosome segregation and the breakdown of the cytoskeletal mesh for cell division.

Microtubule Growth and Shrinkage

mitosis and cytokinesis

Mitosis and Cytokinesis Stages

Mitosis and cytokinesis are the two main steps of cell division. Mitosis is the process that divides the nucleus, while cytokinesis splits the rest of the cell. During mitosis, the cell’s genetic material is separated into two sets. This helps form two new nuclei with the same genetic information. Cytokinesis then completes division by separating the cytoplasm, which creates two daughter cells. These stages work together to make cell division possible in growing and repairing tissues.

duplication of chromatin structure

Chromatin Rebuilding During DNA Replication

Chromatin rebuilding during DNA replication helps cells copy DNA and pass on chromosome structure to daughter cells. During cell division, the genome must be disrupted and then reassembled across the whole chromosome. This process allows chromatin to be inherited, rebuilt, and maintained in new cells. The basic unit of chromatin is the nucleosome. A nucleosome contains DNA wrapped around an octamer of histone proteins, with short linker DNA between neighboring nucleosomes. The histone proteins...

cohesins

Cohesins in Meiosis and Genetic Disorders

Cohesin protein complexes act like molecular glue that keeps sister chromatids together. They are important in both mitosis and meiosis. In mitosis, cohesin complexes are removed from chromosomes before anaphase begins. Meiosis has two rounds of chromosome separation. Meiosis I separates homologous chromosomes, while Meiosis II separates sister chromatids. This process produces four daughter cells. The Meiosis I cohesin complex is made of four subunits: Smc1, Smc3, Rec8, and Scc3. Rec8...

condensins

How Condensins Shape Mitotic Chromosomes

Condensins shape chromosomes during mitosis, the stage when a cell divides. These large protein complexes use ATP, the cell’s energy molecule, to help turn loose post-interphase DNA into compact, separate chromosomes. They organize and segregate chromosomal DNA so it can be passed on correctly. Plant and animal cells contain two condensin complexes: condensin I and condensin II. Each complex has five subunits. Two are SMC, or Structural Maintenance of Chromosomes, subunits. One is a kleisin...

the mitotic spindle

How the Mitotic Spindle Separates Chromosomes

The mitotic spindle is a microtubule-based structure that helps separate chromosomes during cell division. It forms in eukaryotic cells and moves sister chromatids to opposite ends of the parent cell. This leaves each new cell nucleus with the correct genetic material. A bipolar spindle has two poles, and that shape is important for chromosome segregation. In many animal cells, two centrosomes are present when mitosis begins. Each centrosome helps organize a circular set of microtubules at one...

centrosome duplication

Centrosome Duplication in the Cell Cycle

Centrosome duplication is a key part of the animal cell cycle. The centrosome is the main microtubule organizing center, or MTOC, in animal cells. It contains two cylindrical centrioles at its core. Each centriole has nine sets of three microtubules held together by proteins. The two centrioles sit at right angles and are surrounded by the pericentriolar matrix, or PCM, a shapeless protein cloud. Duplication starts early in the cell cycle so each daughter cell can receive a centrosome after...

microtubule instability

Microtubules are hollow, cylindrical filaments in the cell. They are about 25 nm wide and can range from 200 nm to 25 μm in length. Their main building blocks are GTP-bound tubulin subunits that form αβ-heterodimers, which then assemble into protofilaments. These protofilaments join by lateral bonds to create stable microtubule cylinders. Microtubules are highly dynamic because they repeatedly assemble and break down. They can even grow on one end while shrinking on the other at the same time.

spindle assembly

How the Mitotic Spindle Forms

The mitotic spindle forms through centrosome-mediated, chromatin-mediated, and microtubule-mediated pathways. These pathways often work at the same time. Together, they build a strong spindle apparatus for cell division. In most cells, centrosomes are the main sites where microtubules begin to grow. During the G2 to prophase transition, centrosomes mature and make more microtubules. The growing microtubules extend from both centrosomes, and their plus-ends search for chromosomes by attaching...

attachment of sister chromatids

Kinetochore-Microtubule Binding in Mitosis

Kinetochore-microtubule binding helps chromosomes line up and separate during mitosis. After the nuclear envelope breaks down, condensed chromosomes are exposed to the bipolar microtubules of the mitotic spindle. The kinetochore is a large, disc-shaped protein complex at the centromere region of each sister chromatid, and it serves as the microtubule binding site. Usually, the plus-end of a single microtubule inserts into the kinetochore. In some cases, a kinetochore first makes lateral...

forces acting on chromosomes

Chromosome Movement During Mitosis

Chromosome movement during mitosis depends on several small forces that act at different times and positions in the cell. In prometaphase, these forces help chromosomes move to the equatorial plane and line up at the metaphase plate. Because the forces change with location and stage, chromosome behavior also changes as mitosis continues. Microtubules and motor proteins create two main kinds of force on chromosomes: poleward force and anti-poleward force, also called polar-ejection force.

separation of sister chromatids

Anaphase Start and Chromatid Release

Anaphase starts when sister chromatids are released from one another and pulled toward opposite spindle poles. Before that happens, cohesion along the chromosomal arms is reduced from prophase to metaphase, which helps the sister chromatids resolve. A residual cohesin link still holds them together until the metaphase-to-anaphase transition. This leftover connection helps prevent early separation and reduces the risk of aneuploidy, or the wrong number of chromosomes, in daughter cells. At the...

the spindle assembly checkpoint

How Cells Safeguard Chromosome Separation

The spindle assembly checkpoint helps cells safeguard chromosome separation during anaphase. It acts as a molecular surveillance system. The checkpoint checks whether the steps needed for chromosome segregation are complete before the cell moves on. Many proteins work together to control this checkpoint. If mutations affect these proteins, a cell may enter anaphase too early. Chromosomes can then separate before the needed steps are finished. When this happens, the daughter cells may receive...

anaphase a and b

Chromatid Movement by Microtubule Forces

Chromatid movement during anaphase depends on microtubule forces at the spindle. Kinetochore microtubules grow from the spindle poles, and their plus ends attach to kinetochores on sister chromatids. The kinetochore protein complex Ndc80 makes low-affinity links with the microtubule plus end.

the contractile ring

How Cells Build the Contractile Ring

Contractile rings are built from microfilaments and help separate daughter cells during cytokinesis. This ring forms as the cell cycle moves forward, but the exact timing and coordination with other cell cycle events are still not fully understood. RhoA, a small GTPase in the Ras superfamily, controls contractile ring assembly and function. The inactive form of RhoA is bound to GDP. A guanine nucleotide exchange factor, or Rho-GEF, is located in the cortex region, where the next cell division...

determining the plane of cell division

How Cells Set the Division Plane

How cells set the division plane during cell division affects daughter cell size and, in many cases, cell fate. The plane of division is perpendicular to the plane of chromosome segregation. Different organisms use different cues to place it, based on their shape and needs. In animal cells, the cleavage furrow forms along the division plane from the cell cortex, the area just below the plasma membrane. The mitotic spindle is the main guide for this position. If the spindle axis changes, the...

the phragmoplast

How Plant Cells Build a New Wall

Plant cells build a new wall during cytokinesis with help from the phragmoplast. This plant structure forms from the central spindle and related cell parts as the cell finishes dividing. In animal cells, the comparable structure is the midbody, but in plants the phragmoplast expands outward to guide new wall formation. The mature phragmoplast has a donut-like shape. It has an outer leading region, a middle transition zone, and an inner lagging region. New microtubules are assembled...

distribution of cytoplasmic content

How Organelles Are Split During Cytokinesis

Cytokinesis splits a cell’s chromosomes and organelles into two daughter cells. Before cell division, organelles grow and divide. They cannot be made from scratch, so each daughter cell must inherit at least one copy to survive. Many details of this organelle sorting process are still not fully known. The cytoplasm contains organelles, salts, proteins, and water. Small organelles such as peroxisomes and lysosomes can be shared by simple diffusion. Because cells contain many copies of these...

anaphase promoting complex

APC Activates Chromosome Separation

The anaphase-promoting complex, or APC, helps control cell cycle progression by destroying specific proteins at the right time. These proteins are tagged with ubiquitin by ubiquitin ligases and then broken down by the proteasome. The SCF (Skp1/Cullin/F-box) complex and APC are two major ubiquitin ligases involved in this process. SCF stays active throughout the cell cycle, but APC turns on during the metaphase-to-anaphase transition. APC becomes active when Cdc20 or Cdh1 binds to it. These...

key terms and concepts

Explore how microtubules grow, shrink, and switch states through catastrophe, rescue, GTP hydrolysis, and MAP control in cells.

Microtubule Growth and Shrinkage | JoVE K12

molecular biology

JoVE Core 분자생물학은 명확하고 간결한 애니메이션을 통해 분자 단계에서 일어나는 세포 과정을 설명합니다.또한, 과학자가 직접 실험을 진행하는 실사 영상을 통해 분자생물학 개념의 응용 사례를 보여줍니다.

Microtubule Growth and Shrinkage

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