Essential Cell Biology 5th edition

Enzyme-Coupled Receptors
565
unspecified
epithelial cells
CELL
SPECIALIZATION
AND
LATERAL
INHIBITION
membrane-bound
inhibitory signal
protein (Delta)
nerve cell
developing from
epithelial cell
receptor
protein
(Notch)
inhibited
epithelial cell
Figure 16–38 Notch signaling controls
nerve-cell production in the fruit fly
Drosophila. The fly nervous system
originates in the embryo from a sheet of
epithelial cells. Isolated cells in this sheet
begin to specialize as neurons (blue), while
their neighbors remain non-neuronal and
maintain the structure of the epithelial
sheet. The signals that control this process
are transmitted via direct cell–cell contacts:
each future neuron delivers an inhibitory
signal to the cells next to it, deterring them
from specializing as neurons too—a process
called lateral inhibition. Both the signal
molecule (Delta) and the receptor molecule
(Notch) are transmembrane proteins, and
the pathway represents a form of contactdependent
signaling (see Figure 16−3D).
Some Receptors Activate a Fast Track to the Nucleus
ECB5 e16.04/16.38
Not all receptors trigger complex signaling cascades that use multiple
components to carry a message to the nucleus. Some take a more direct
route to control gene expression. One such receptor is the protein Notch.
Notch is a crucially important receptor in all animals, both during development
and in adults. Among other things, it controls the development
of neural cells in Drosophila (Figure 16–38).
In this simple signaling pathway, the receptor itself acts as a transcription
regulator. When activated by the binding of Delta, a transmembrane
signal protein on the surface of a neighboring cell, the Notch receptor is
cleaved. This cleavage releases the cytosolic tail of the receptor, which is
then free to move to the nucleus, where it helps to activate the appropriate
set of Notch-responsive genes (Figure 16–39).
Some Extracellular Signal Molecules Cross the Plasma
Membrane and Bind to Intracellular Receptors
Another direct route to the nucleus is taken by extracellular signal molecules
that rely on intracellular receptor proteins (see Figure 16–4B).
These molecules include the steroid hormones—cortisol, estradiol, and
testosterone—and the thyroid hormones such as thyroxine (Figure 16–40).
All of these hydrophobic molecules pass through the plasma membrane
developing nerve cell
Delta
signal protein
Delta receptor
(Notch)
DELTA BINDS
TO NOTCH
plasma
membranes
CYTOSOL
NUCLEUS
neighboring cell
TRANSCRIPTION OF
NOTCH-RESPONSIVE
GENES
cleaved
Notch tail
migrates to
nucleus
Figure 16–39 The Notch receptor
itself is a transcription regulator. When
the membrane-bound signal protein
Delta binds to its receptor, Notch, on a
neighboring cell, the receptor is cleaved
by a protease. The released part of the
cytosolic tail of Notch migrates to the
nucleus, where it activates Notch-responsive
genes. One consequence of this signaling
process is shown in Figure 16−38.