Transmembrane Signal Transmitters

Functional signals between cells are received by
transmembrane proteins as signal transmitters.
During evolution, relatively simple precursor
genes for such proteins gave rise to multiple
structurally and functionally related genes.
Their corresponding proteins serve to transmit
ions (sodium, potassium, calcium, chloride, and
others), as neurotransmitters, and for perception
of light and odors, etc. Cloning of these
genes has yielded insight into the variety of
functions of transmembrane signal transmitters.
Their general structure can be traced back
to an evolutionarily conserved ancestral
molecule.

Transmembrane structure of voltage-gated ion channels

The direct flowof ions across the cell membrane
is regulated by ion channels. The transmembrane
proteins, composed of several domains,
are arranged so that they form pores that can be
opened and closed. The simplest model is the
potassium channel (1). This membrane-bound
polypeptide contains six transmembrane
domains. The amino and the carboxy ends of
the protein lie within the cell. Changes in cell
membrane potential or voltage cause the channel
to open (or close) in order to initiate (or terminate)
a brief flow of ions. Domain 4, which is
composed of polar amino acids, is crucial for the
flow of ions. Sodium and calcium ion channels
consist of four subunits (2) of similar structure,
each resembling a potassium channel. The similarity
is due to the common evolutionary origin
of their genes. The four subunits of the sodium
channel (3) are positioned to form a very narrow
porelike passage, much narrower than a
potassium channel, through the plasma membrane.
Ion transport is brought about by membrane
depolarization

Seven-helix structure of transmembrane signal transmitters

Indirect transmission of signals is more
frequent than the direct transport of ions or ligand-
gated impulse transmission. Here, the
transmembrane protein is involved only in the
first step of signal transmission.

common structural motif is a transmembrane protein

An especially common structural motif
is a transmembrane protein containing seven !
helices within the plasma membrane. The
amino end is extracellular; the carboxy end is
intracellular. Different oligosaccharide side
chains are usually bound to the extracellular
domains. The intracellular domains have binding
sites for other molecules involved in signal
transmission. The seven-helix motif is the
characteristic structure of G protein-binding receptors
(p. 268). As the G proteins themselves,
these receptors and their genes form a large
family with a long evolutionary history. In
yeast, they serve to discern the pheromones of
the mating types (p. 186); in higher organisms
they are the basis for transmitting signals of vision,
smell, and taste

A receptor with two transmembrane protein chains,

The receptor for "-aminobutyric acid (GABA)
utilizes two transmembrane protein subunits, !
and #. Both the amino and the carboxy ends are
extracellular. The two chains are coded for by
different genes. Several oligosaccharide side
chains are present on the extracellular side. The
# chain contains a phosphorylation site for
cAMP-dependent protein kinase.

Receptors of Neurotransmitters

Impulses are relayed between nerve cells or between
nerve and muscle cells by various transmitter
molecules (neurotransmitters). Their effects
are further relayed by receptors in the cell
membrane. Receptors can be differentiated according
to their structure, which in turn determines
their specificity.

Acetylcholine as a neurotransmitter

Cholinergic synapses convey the nerve impulse
from one nerve cell to another or from a nerve
cell to a muscle cell (motor endplate). Acetylcholine
leads to postsynaptic depolarization
through the release of potassium ions (K+) and
the uptake of sodium ions (Na+). This process is
regulated by an acetylcholine receptor.