Rhodopsin, a Photoreceptor

The human retina contains about 110 million
rod cells for vision in the dark and 6 million
cone cells for color vision in the light. These
cells contain photoreceptors that convert light
into a nerve impulse. Rhodopsin is the photoreceptor
for weak light. The light-transmitting
system consists of numerous components
coded for by genes that are similar in structure
and function to genes for other transmembrane
signal-transmitting molecules.

A. Rod cells

A rod cell consists of an outer segment with a
photoreceptor region and an inner segment
comprising cell nucleus and cytoplasm with endoplasmic
reticulum, Golgi apparatus, and mitochondria.
The outer segment contains about
1000 disks with rhodopsin molecules in the
membrane. In the periphery, the approximately
16nm thick disks are folded by the protein peripherin.

Photoactivation

In 1958, George Wald and co-workers discovered
that light isomerizes 11-cis-retinal (1)
very rapidly into all-trans-retinal (2), a form
that practically does not exist in the dark
(!1 molecule/1000 years). The light-induced
structural change is so great that the resulting
atomic motion can trigger a reliable and reproducible
nerve impulse. The absorption spectrum
of rhodopsin (3) corresponds to the spectrum
of sunlight, with an optimum at a
wavelength of 500 nm. Although vertebrates,
arthropods, and mollusks have anatomically
quite different types of eyes, all three phyla use
11-cis-retinal for photoactivation.

Light cascade

Photoactivated rhodopsin triggers a series of
enzymatic steps (light cascade). First, a signaltransmitting
protein of visualization, transducin,
is activated by photoactivated rhodopsin.
Transducin belongs to the G protein family, i.e.,
it can assume an inactive GDP and an active GTP
form. GTP activates phosphodiesterase. This
very rapidly hydrolyzes cGMP and lowers the
cGMP concentration in cytosol, which leads to
closure of the sodium ion channels. Immediately
thereafter, phosphodiesterase is inactivated
by means of a G protein cycle.

Rhodopsin

Rhodopsin is a seven-helix transmembrane
protein with binding sites for functionally important
molecules such as transducin, rhodopsin
kinase, and arrestin on the cytosol side. The
binding site of the light-sensitive molecule
(chromophore) is lysine in position 296 of the
seventh transmembrane domain. The light-absorbing
group consists of 11-cis-retinal. The
amino end of rhodopsin is located in the disk interspaces,
and the carboxy end on the cytosol
side. About half of the molecule is contained in
the seven transmembrane hydrophobic domains,
one-fourth in the disk interspaces and
one-fourth on the cytosol side.

cGMP as transmitter in the vizualization process

The light cascade ends with rapid hydrolysis of
cGMP, the internal transmitter in visualization.
This leads to rapid closure of the sodium ion
channels and hyperpolarization of the membrane
to initiate nerve impulse, which is transmitted
as a signal to the brain.

Mutations in Rhodopsin

Retinitis pigmentosa (RP) is a genetically heterogeneous
group of diseases that lead to
pigmental degeneration of the retina and progressive
blindness. Numerous mutations in the
rhodopsin gene have been shown to be the
cause of different forms of RP. Mutations in
other genes coding for proteins of the light cascade
may also cause retinitis pigmentosa.