Lodish H. - Molecular Cell Biology (5ed, Freeman, 2003) (794361), страница 8
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(a) Binding of ahormone or other signaling molecule to its specific receptorscan trigger an intracellular pathway that increases or decreasesthe activity of a preexisting protein. For example, binding ofinsulin to receptors in the plasma membrane of liver and musclecells leads to activation of glycogen synthase, a key enzyme inthe synthesis of glycogen from glucose. (b) The receptors forsteroid hormones are located within cells, not on the cellsurface. The hormone-receptor complexes activate transcriptionof specific target genes, leading to increased production of theencoded proteins.
Many signals that bind to receptors on thecell surface also act, by more complex pathways, to modulategene expression.tracellular signals, signal receptors, or intracellular signaltransduction proteins, which pass along a signal through aseries of steps culminating in a particular cellular response(e.g., increased glycogen synthesis). Clearly, signaling andsignal transduction are major activities of cells.Cells Regulate Their Gene Expression to MeetChanging NeedsIn addition to modulating the activities of existing proteins,cells often respond to changing circumstances and to signalsfrom other cells by altering the amount or types of proteins theycontain.
Gene expression, the overall process of selectivelyreading and using genetic information, is commonly controlledat the level of transcription, the first step in the production ofproteins. In this way cells can produce a particular mRNA onlywhen the encoded protein is needed, thus minimizing wastedenergy. Producing a mRNA is, however, only the first in a chainof regulated events that together determine whether an activeprotein product is produced from a particular gene.1.3 • The Work of CellsThe most remarkable feature of cells and entire organisms istheir ability to reproduce. Biological reproduction, combinedNondividingcellsRestingcellsG1G0RNA andproteinsynthesisMCelldivisionDNAreplicationSRNA andproteinsynthesisG2▲ FIGURE 1-17 During growth, eukaryotic cellscontinually progress through the four stages of the cellcycle, generating new daughter cells.
In mostproliferating cells, the four phases of the cell cycle proceedsuccessively, taking from 10–20 hours depending on celltype and developmental state. During interphase, whichconsists of the G1, S, and G2 phases, the cell roughlydoubles its mass. Replication of DNA during S leaves thecell with four copies of each type of chromosome. In themitotic (M) phase, the chromosomes are evenly partitionedto two daughter cells, and the cytoplasm divides roughly inhalf in most cases. Under certain conditions such asstarvation or when a tissue has reached its final size, cellswill stop cycling and remain in a waiting state called G0.Most cells in G0 can reenter the cycle if conditions change.MEDIA CONNECTIONSCells Grow and Dividewith continuing evolutionary selection for a highly functionalbody plan, is why today’s horseshoe crabs look much as theydid 300 million years ago, a time span during which entiremountain ranges have risen or fallen.
The Teton Mountains inWyoming, now about 14,000 feet high and still growing, didnot exist a mere 10 million years ago. Yet horseshoe crabs,with a life span of about 19 years, have faithfully reproducedtheir ancient selves more than half a million times during thatperiod. The common impression that biological structure istransient and geological structure is stable is the exact opposite of the truth. Despite the limited duration of our individual lives, reproduction gives us a potential for immortalitythat a mountain or a rock does not have.The simplest type of reproduction entails the division ofa “parent” cell into two “daughter” cells. This occurs as partof the cell cycle, a series of events that prepares a cell to dividefollowed by the actual division process, called mitosis. Theeukaryotic cell cycle commonly is represented as four stages(Figure 1-17). The chromosomes and the DNA they carry arecopied during the S (synthesis) phase.
The replicated chromosomes separate during the M (mitotic) phase, with eachdaughter cell getting a copy of each chromosome during celldivision. The M and S phases are separated by two gap stages,the G1 phase and G2 phase, during which mRNAs and proteins are made. In single-celled organisms, both daughter cellsOverview Animation: Life Cycle of a CellTranscriptional control of gene expression was first decisively demonstrated in the response of the gut bacteriumE.
coli to different sugar sources. E. coli cells prefer glucoseas a sugar source, but they can survive on lactose in a pinch.These bacteria use both a DNA-binding repressor proteinand a DNA-binding activator protein to change the rate oftranscription of three genes needed to metabolize lactose depending on the relative amounts of glucose and lactose present (Chapter 4). Such dual positive/negative control of geneexpression fine tunes the bacterial cell’s enzymatic equipmentfor the job at hand.Like bacterial cells, unicellular eukaryotes may be subjected to widely varying environmental conditions that require extensive changes in cellular structures and function.For instance, in starvation conditions yeast cells stop growing and form dormant spores (see Figure 1-4).
In multicellular organisms, however, the environment around most cells isrelatively constant. The major purpose of gene control in usand in other complex organisms is to tailor the properties ofvarious cell types to the benefit of the entire animal or plant.Control of gene activity in eukaryotic cells usually involves a balance between the actions of transcriptional activators and repressors. Binding of activators to specific DNAregulatory sequences called enhancers turns on transcription,and binding of repressors to other regulatory sequencescalled silencers turns off transcription. In Chapters 11 and12, we take a close look at transcriptional activators and repressors and how they operate, as well as other mechanismsfor controlling gene expression.
In an extreme case, expression of a particular gene could occur only in part of thebrain, only during evening hours, only during a certain stageof development, only after a large meal, and so forth.Many external signals modify the activity of transcriptional activators and repressors that control specific genes.For example, lipid-soluble steroid hormones, such as estrogen and testosterone, can diffuse across the plasma membrane and bind to their specific receptors located in thecytoplasm or nucleus (Figure 1-16b). Hormone bindingchanges the shape of the receptor so that it can bind to specific enhancer sequences in the DNA, thus turning the receptor into a transcriptional activator. By this rather simplesignal-transduction pathway, steroid hormones cause cells tochange which genes they transcribe (Chapter 11).
Sincesteroid hormones can circulate in the bloodstream, they canaffect the properties of many or all cells in a temporally coordinated manner. Binding of many other hormones and ofgrowth factors to receptors on the cell surface triggers different signal-transduction pathways that also lead to changesin the transcription of specific genes (Chapters 13–15). Although these pathways involve multiple components and aremore complicated than those transducing steroid hormonesignals, the general idea is the same.1718CHAPTER 1 • Life Begins with Cellsoften (though not always) resemble the parent cell.
In multicellular organisms, stem cells can give rise to two differentcells, one that resembles the parent cell and one that does not.Such asymmetric cell division is critical to the generation ofdifferent cell types in the body (Chapter 22).During growth the cell cycle operates continuously, withnewly formed daughter cells immediately embarking on theirown path to mitosis. Under optimal conditions bacteria can divide to form two daughter cells once every 30 minutes.
At thisrate, in an hour one cell becomes four; in a day one cell becomes more than 1014, which if dried would weigh about 25grams. Under normal circumstances, however, growth cannotcontinue at this rate because the food supply becomes limiting.Most eukaryotic cells take considerably longer than bacterial cells to grow and divide. Moreover, the cell cycle in adultplants and animals normally is highly regulated (Chapter 21).This tight control prevents imbalanced, excessive growth oftissues while assuring that worn-out or damaged cells are replaced and that additional cells are formed in response to newcircumstances or developmental needs.
For instance, the proliferation of red blood cells increases substantially when a person ascends to a higher altitude and needs more capacity tocapture oxygen. Some highly specialized cells in adult animals,such as nerve cells and striated muscle cells, rarely divide, ifat all. The fundamental defect in cancer is loss of the abilityto control the growth and division of cells. In Chapter 23, weexamine the molecular and cellular events that lead to inappropriate, uncontrolled proliferation of cells.Mitosis is an asexual process since the daughter cellscarry the exact same genetic information as the parental cell.In sexual reproduction, fusion of two cells produces a thirdcell that contains genetic information from each parentalcell.
Since such fusions would cause an ever-increasing number of chromosomes, sexual reproductive cycles employ aspecial type of cell division, called meiosis, that reduces thenumber of chromosomes in preparation for fusion (see Figure 9-3). Cells with a full set of chromosomes are calleddiploid cells. During meiosis, a diploid cell replicates its chromosomes as usual for mitosis but then divides twice withoutcopying the chromosomes in-between. Each of the resultingfour daughter cells, which has only half the full number ofchromosomes, is said to be haploid.Sexual reproduction occurs in animals and plants, andeven in unicellular organisms such as yeasts (see Figure 1-5).Animals spend considerable time and energy generating eggsand sperm, the haploid cells, called gametes, that are used forsexual reproduction.
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