Introduction 
ually being formed and replaced. Other cells pro- 
liferate rarely, and some divide only during early 
development; the nerve cells that make up the 
brain, for example, proliferate rapidly during de- 
velopment, but no further cell division occurs 
until death some 70 or more years later. Obvi- 
ously, cell proliferation must be tightly con- 
trolled. Recent advances have shown that the cell 
cycle is controlled 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 phosphate 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 con- 
trol 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 li- 
gand-binding domain that can bind the hormone 
or diffusible factor, a transmembrane domain that 
spans the cell membrane, and an intracellular 
part that can interact with internal components of 
the cell. The binding of a hormone or other diffu- 
sible factor to such a receptor triggers in some 
way, as yet undetermined, a signal 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 dif- 
fusible, small molecules, such as calcium ions or 
cyclic nucleotides. These diffusible second mes- 
senger molecules in turn activate other control 
mechanisms inside the cell, including protein ki- 
nases and other regulatory molecules. In this way 
the triggering of a receptor from outside cells can 
result in a cascade of events that ultimately con- 
trols the various intracellular processes discussed 
earlier. One of the current "hot topics" in cell 
biology research concerns the nature and mecha- 
nisms of cell surface receptor signaling and the 
control circuits inside cells that link receptor ac- 
tivity to other control mechanisms, including 
those that regulate 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 
intracellular message. Since the majority of 
nerve signals are transmitted from cell to cell 
in this way, the analysis of this class of recep- 
tors is (as we shall see in the section on neuro- 
science) one of the central issues in contem- 
porary 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 
epidermis 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 
this case, the extracellular matrix helps to pro- 
vide the body's architectural framework. 
Cellular adhesion, which plays a crucial role in 
cell, tissue, and organ structure and in cell move- 
ments, depends on sp)ecialized cell adhesion recep- 
tors that are conneaed to the intracellular cytoskele- 
ton. It is also likely that cells can signal to one 
another via cell adhesion receptors. Decisions as to 
whether a cell remains stationary, or where and 
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