A membranous spindle matrix orchestrates cell division - PubMed (original) (raw)
Review
A membranous spindle matrix orchestrates cell division
Yixian Zheng. Nat Rev Mol Cell Biol. 2010 Jul.
Abstract
Eukaryotic cell division uses morphologically different forms of mitosis, referred to as open, partially open and closed mitosis, for accurate chromosome segregation and proper partitioning of other cellular components such as endomembranes and cell fate determinants. Recent studies suggest that the spindle matrix provides a conserved strategy to coordinate the segregation of genetic material and the partitioning of the rest of the cellular contents in all three forms of mitosis.
Conflict of interest statement
Competing interests statement
The authors declare no competing financial interests.
Figures
Figure 1. Metaphase spindles in three forms of mitosis
Eukaryotes have evolved various forms of mitosis to coordinate nuclear morphogenesis with mitotic spindle assembly. a | Closed mitosis, which is found in lower eukaryotes such as the fungus Saccharomyces cerevisiae, refers to mitosis in which nuclear envelope does not breakdown during spindle assembly and chromosome segregation. Spindle pole bodies (not shown) embedded in the nuclear envelope nucleate cytoplasmic microtubules, which interact with the cell cortex, and nuclear microtubules, which interact with one another or kinetochores of chromosomes. After chromosome segregation, the nucleus undergoes karyokinesis to form two daughter nuclei (not shown). b | An example of partially open mitosis can be found in Drosophila melanogaster early syncytial embryos, in which all nuclei occupy the same cytoplasm. During mitosis, plasma membrane invaginations (small arrows) separate spindles formed by different nuclei. Two adjacent nuclei undergoing mitosis are depicted. The microtubules nucleated from the centrosomes invade the nuclear space through two openings on the nuclear envelope to form spindles that are surrounded by the nuclear envelope. During anaphase, the nuclear envelope undergoes further disassembly and is then reassembled during telophase (not shown). c | The assembly of the mitotic spindle during open mitosis, found in vertebrates, is accompanied by a complete disassembly of the nuclear envelope during prometaphase (for more details, see BOX 1).
Figure 2. Two types of spindle matrices in open mitosis, as revealed by physical perturbations
a | An elastic spindle matrix surrounds spindle microtubules, as revealed by cutting a few kinetochore microtubules in a metaphase spindle by ultraviolet (Uv) irradiation. After irradiating one half of the spindle (top half), the uncut microtubules in this half curve back, causing shortening of the half spindle. This suggests that the elastic spindle matrix is normally stretched by spindle microtubules. When this stretching force is reduced, the spindle matrix would collapse onto spindle microtubules, causing them to bend and buckle. An elastic and continuous spindle matrix that permeates the spindle microtubules could also carry out the same function but has been omitted from this figure for simplicity. The arrows in the right panel show the direction of the compression force from the contracting matrix that causes the shrinking of the half spindle. b | A speculative spindle matrix aligns along kinetochore microtubules. UV irradiation of the indicated kinetochore microtubule did not block this kinetochore from moving to spindle poles during anaphase of insect cell mitosis. The arrow in the right panel shows the direction of movement of the kinetochore with a microtubule stub.
Figure 3. Localization of spindle matrix components
a | The Drosophila melanogaster spindle matrix. The nuclear proteins skeletor, Megator, East and chromator interact with each other to form an internal spindle matrix that colocalizes with microtubules of the spindle throughout mitosis in D. melanogaster syncytial embryos. The organization of these proteins in the matrix is currently unknown, but after microtubule disassembly by microtubule depolymerization drugs such as nocodazole, this network remains intact. One function of the D. melanogaster spindle matrix is to tether the spindle assembly checkpoint proteins MAD1 (also known as TXBP181) and MAD2 to facilitate their binding to kinetochores. This internal spindle matrix is surrounded by a spindle envelope containing lamin B and the nuclear membrane. The spindle envelope has recently been shown to function as an elastic spindle matrix. b | The spindle pole matrix formed by poly−ADP ribose−modified nuclear mitotic apparatus protein (NUMA) in vertebrates that carry out open mitosis. NUMA localizes to the nucleus in interphase (not shown). In mitosis, poly−ADP ribose polymerase 5A (PARP5A; also known as tankyrase 1) catalyses the covalent modification of NUMA by poly−ADP ribose. Modified NUMA is transported to the minus ends of microtubules in early prometaphase, when the nuclear envelope starts to breakdown (left), to assemble into a network to facilitate the interactions of microtubule minus ends to form focused spindle poles (right). c | Lamin B spindle matrix localizes to spindles assembled from sperm chromatin (left) or Aurora A beads (centre; green). Aurora A spindles were treated with nocodazole and, after microtubule depolymerization, the spindle matrix that remains associated with Aurora A beads was stained using antibodies to lamin B and dynein (right panels; Aurora A beads in green and red). Right and left panels in part c are reproduced, with permission, from Nature Cell Biology REF. © (2009) Macmillan Publishers. All rights reserved.
Figure 4. A unified model of the spindle matrix in patterning cell division
All forms of mitosis can use the spindle matrix to coordinate chromosome segregation with the partitioning of the rest of the cellular components into daughter cells. a | The mitotic nucleus functions as a spindle matrix in closed mitosis. The mitotic nuclear envelope, through its connection with the endoplasmic reticulum (ER), could help partition various cellular components such as the endomembrane system during cell division. b | The spindle matrix in partially open mitosis includes the nuclear envelope, nuclear lamina and the intra−nuclear spindle matrix, which contains Megator, skeletor, chromator and East. This network may organize nuclear content and cytoplasmic membranes for proper division. c | In open mitosis, dynein and its regulator Nudel regulate assembly of membranous lamin B spindle matrix in a microtubule and RAN–GtP−dependent manner. This spindle matrix contains nuclear mitotic apparatus protein (NUMA) and poly−ADP ribose (not shown). Similar to spindle matrix in closed and partially open mitosis, the lamin B−containing matrix associates with the spindle to organize nuclear contents and cytoplasmic membranes, coordinating their partitioning into daughter cells.
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