As discussed in Chapter 16 the principal microtubule organizing center (MTOC) in most animal

2 As discussed in Chapter 16 the principal microtubule organizing center (MTOC) in most animal

cells is the centrosome, a cloud of poorly defined pericentriolar material (the centrosome matrix) associated with a pair of centrioles (Figure 18-3). During interphase the centrosome matrix nucleates a cytoplasmic array of microtubules, which project outward toward the cell perimeter with their minus ends attached to the centrosome. Before a eucaryotic cell divides, it must duplicate its centrosome to provide one for each of its two daughter cells. In fact, duplicated cells is the centrosome, a cloud of poorly defined pericentriolar material (the centrosome matrix) associated with a pair of centrioles (Figure 18-3). During interphase the centrosome matrix nucleates a cytoplasmic array of microtubules, which project outward toward the cell perimeter with their minus ends attached to the centrosome. Before a eucaryotic cell divides, it must duplicate its centrosome to provide one for each of its two daughter cells. In fact, duplicated

Centrosomes in most animal species share a remarkable and distinctive structural feature in the form of a pair of centrioles (discussed in Chapter 16). The centrioles, however, which are associated with the centrosome matrix, are not required for the nucleation of microtubules: plant centrosomes lack centrioles altogether, and centrioles are also missing during the early divisions of the cleaving mouse egg; moreover, drug treatments of cultured mammalian cells can create tripolar mitotic spindles, in which one spindle pole lacks centrioles yet appears to function normally. It is therefore thought that the centrosome matrix, which contains a set of centrosome- specific proteins, is the most fundamental part of the centrosome. When present, the centrioles associated with the matrix are duplicated in a strictly ordered manner, and their behavior may help in the creation of precisely two centrosomes as the cell enters each M phase (Figure18-4).

The process of centrosome duplication and separation is known as the centrosome cycle. During interphase of each cell cycle, the centrioles and other components of the centrosome are duplicated but remain together as a single complex on one side of the nucleus. As mitosis begins, this complex splits in two and each centriole pair becomes part of a separate microtubule organizing center that nucleates a radial array of microtubules called an aster. The two asters move to opposite sides of the nucleus to form the two poles of the mitotic spindle. As mitosis ends and the nuclear envelope re-forms around the separated chromosomes, each daughter cell receives a centrosome (the former spindle pole) in association with its chromosomes (Figure 18- 5).

The centrosome cycle can operate with a surprising degree of independence from other processes of the cell cycle. Thus, if the nucleus is physically removed from a sea urchin egg, or if nuclear DNA replication is blocked by the DNA synthesis inhibitor aphidicolin, cycles of centrosome doubling and division proceed almost normally, giving first two centrosomes, then four, then eight. And in early Drosophila embryos similarly treated with aphidicolin, the proliferating centrosomes in the interior of the embryo dissociate from their blocked nuclei and march stepwise through the cytoplasm toward the plasma membrane; once they reach this membrane the centrosomes, through their asters, can reshape the membrane and its underlying cortex, generating cells that contain centrosomes but no nuclei (Figure 18-6). Cleaving eggs, with their stockpiles of cell components that free them from dependence on gene transcription, are admittedly exceptional in their behavior; in other cells the centrosome cycle depends on the presence of a functional cell nucleus. Yet it is clear that the division cycle of the cell as a whole depends on - and is at least in part organized by - the microtubule aster, which is in turn organized by the centrosome.

Centrosomes, and the centrioles usually associated with them, have perplexed and tantalized cell biologists for more than a hundred years. What are they made of, how are they replicated, and how did they originate in the course of evolution? These fundamental questions remain to be answered.

M P h a s e I s Tra d it io n a lly D iv id e d in t o S ix S t a g e s

The basic strategy of cell division is remarkably constant among eucaryotic organisms. The first five stages of the M phase constitute mitosis (originally defined as the period in which the The basic strategy of cell division is remarkably constant among eucaryotic organisms. The first five stages of the M phase constitute mitosis (originally defined as the period in which the

The description of cell division is based on observations from two sources: light microscopy of living cells (often combined with microcinematography) and light and electron microscopy of fixed and stained cells. A brief summary of the various stages of cell division is given in Panel18-1. The five stages of mitosis - prophase, prometaphase, metaphase, anaphase, and telophase - occur in strict sequential order, while cytokinesis begins during anaphase and continues through the end of M phase (Figure18-7). Light micrographs of cell division in a typical animal and a typical plant cell are shown in Figures18-8 and 18-9, respectively. Innumerable variations in all of the stages of cell division shown schematically in Panel 18-1 occur in the animal and plant kingdoms. We shall mention some of these after we have looked more closely at the general mechanisms of cell division.

La rg e Cy t o p la s m ic Org a n e lle s Are Fra g m e n t e d D u rin g M

P h a s e t o En s u re Th a t Th e y Are Fa it h fu lly I n h e rit e d 3

The process of cell division must ensure that all the essential classes of cell components are inherited by each daughter cell. As discussed in Chapter 12organelles like mitochondria and chloroplasts, for example, cannot assemble spontaneously from their individual components; they can arise only from the growth and fission of the corresponding preexisting organelle, and a daughter cell cannot contain any unless it has inherited one or more. Likewise, it may not be possible to make new copies of the Golgi apparatus and endoplasmic reticulum without the prior presence of at least part of the corresponding structure. How are the various membrane-bounded organelles segregated when a higher eucaryotic cell divides? Organelles present in very large numbers will be safely inherited if, on average, their numbers simply double once each cell generation. Other organelles, such as the Golgi apparatus and the endoplasmic reticulum (ER), break up into a set of smaller fragments and vesicles during mitosis, presumably because in this highly vesiculated form they can be more evenly distributed when a cell divides. The ER vesicles seem to associate with microtubules of the mitotic spindle, which may help distribute them evenly between the two daughter cells.