Introduction 
formation of a nucleus in each of the daughter 
cells, and finally the resumption of normal func- 
tion in both cells. This whole process, which is 
known as the cell cycle, takes place whenever 
cells divide and remains an important part of the 
life of all but a few cell types. Many types of cells 
^for example, the cells in the blood and skin — 
are continually being formed and replaced. 
Other cells proliferate rarely, and some divide 
only during early development; the nerve cells 
that make up the brain, for example, proliferate 
rapidly during development, but no further cell 
division occurs before death of the individual 
some 70 or more years later. Obviously, cell pro- 
liferation must be tightly controlled. Recent ad- 
vances have shown that the cell cycle is con- 
trolled by a set of proteins whose role is to modify 
other proteins selectively and thus regulate their 
functions. One common way in which proteins 
are modified (but certainly not the only one) is to 
attach a small chemical group, such as a phos- 
phate group, to a protein. Proteins that attach 
phosphate groups to other proteins are called 
protein kinases. Control of many aspects of the 
cell cycle and, indeed, of many other cellular 
functions relies on complex control networks of 
protein kinases acting on key proteins at pivotal 
stages in the life of the cell. 
Thus far we have considered only processes oc- 
curring within a cell. An important related set of 
issues concerns how cells interact with each 
other and how they respond to the external envi- 
ronment. Each cell is surrounded by a surface 
(or plasma) membrane, which serves as a se- 
lective barrier separating the inside of the cell 
from the world outside itself. Embedded in this 
membrane are several types of proteins. One es- 
sential class are transporters, specialized for 
the ordered movement in and out of the cell of 
nutrients, ions and other small molecules that are 
essential for normal cell function. 
A second group of cell surface proteins are re- 
ceptors, which bind other types of molecules 
that interact with the cell. As the name suggests, 
receptors serve to receive input from the cell's 
external environment. They are of many different 
types. The largest group binds peptide hormones 
or diffusible factors produced locally or at a dis- 
tance by other cells, but another important group 
serves to transport materials like cholesterol from 
outside to the interior of the cell. Typically these 
receptors have three parts: an external part or 
ligand-binding domain that can bind the hor- 
mone or diffusible factor, a transmembrane do- 
main that spans the cell membrane, and an intra- 
cellular part that can interact with internal 
components of the cell. The binding of a hor- 
mone or other diffusible factor to such a receptor 
triggers in some way, as yet undetermined, a sig- 
nal inside the cell. These signals are of many 
types. Some receptors are protein kinases that are 
selectively activated by binding the appropriate 
external factor; others, when activated, lead to 
the release of diffusible, small molecules, such as 
calcium ions or cyclic nucleotides. These diffusi- 
ble second messenger molecules in turn acti- 
vate other control mechanisms inside the cell, 
including protein kinases and other regulatory 
molecules. In this way the triggering of a recep- 
tor from outside cells can result in a cascade of 
events that ultimately controls the various intra- 
cellular processes discussed earlier. One of the 
current "hot topics" in cell biology research 
concerns the nature and mechanisms of cell sur- 
face receptor signaling and the control circuits 
inside cells that link receptor activity to other 
control mechanisms, including those that regu- 
late gene function and the control of the cell 
cycle. 
A special subset of this class of receptors are 
those that respond to the release of chemical sig- 
nals (transmitters) at the specialized endings of 
nerve cell processes (Figure 7) . The released neu- 
rotransmitters bind to the external part of the cell 
surface receptor and in doing so may open an ion 
channel or trigger the activation of a second in- 
tracellular message. Since the majority of nerve 
signals are transmitted from cell to cell in this 
way, the analysis of this class of receptors is (as 
we shall see in the section on neuroscience) 
one of the central issues in contemporary 
neuroscience. 
Another class of cell surface receptors is in- 
volved in the adhesion of cells, either to their 
neighbors or to the extracellular matrix, a 
complex group of secreted proteins and polysac- 
charides that assemble into an organized mesh- 
work on the cell surface. Depending upon the 
cell type and environment, the extracellular ma- 
trix performs various functions (Figure 8). In a 
petri dish, for example, the extracellular matrix 
provides a cushion on which the cell sits. In the 
epidermis, the extracellular matrix helps to form 
the basement membrane, which anchors the epi- 
dermis to the rest of the skin. In connective 
tissues, the extracellular matrix completely 
surrounds most cells and is often more extensive 
in its distribution than the cells themselves. In 
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