Biology Reference
In-Depth Information
prokaryotes, are sufficiently different from eukaryotes to present a variety of anti-bacterial
approaches not amenable to fungi. However, Fungi do have an Achilles Heel. Fungal plasma
membranes have as their dominant sterol ergosterol, not the animal sterol cholesterol (see
Chapter 5). Nystatin binds preferentially to ergosterol, thus targeting fungi in the presence
of animal cells. When present in sufficient levels, nystatin complexes with ergosterol and
forms trans-membrane channels that lead to K
þ
leakage and death of the fungus. Nystatin
is a polyene anti-fungal ionophore that is effective against many molds and yeast including
Candida. A major use of nystatin is as a prophylaxis for AIDS patients who are at risk for
fungal infections.
F. GAP JUNCTIONS
Gap junctions are a structural feature of many animal plasma membranes
[39,40]
. In plants
similar structures are known as plasmodesmata. Gap junctions were introduced earlier in
Chapter 11 (see Figure 11.6). Gap junctions represent a primitive type of intercellular commu-
nication that allows trans-membrane passage of small solutes like ions, sugars, amino acids,
and nucleotides while preventing migration of organelles and large polymers like proteins
and nucleic acids. Gap junctions connect the cytoplasms of two adjacent cells through
non-selective channels. Connections through adjacent cells are at locations where the gap
between cells is only 2
3 nm. This small gap is where the term 'gap junction' originated.
Gap junctions are normally clustered from a few to over a thousand in select regions of
a cell plasma membrane.
Early experiments involved injecting fluorescent dyes, initially fluorescein (MW 300), into
a cell and observing the dye movement into adjacent cells with a fluorescence microscope
[41,42]
. Currently, Lucifer Yellow has become the fluorescent dye of choice for gap junction
studies, replacing fluorescein. The dye at first only appeared in the initially labeled cell.
With time, however, the dye was observed to spread to adjacent cells through what appeared
to be points on the plasma membrane. These points were later recognized as gap junctions.
By varying the size of the fluorescent dye it was shown that there was an upper size limit for
dye diffusion. Solutes had to have a molecular weight of less than ~1,200 to cross from one
cell to another
[41]
.
Although gap junctions were obviously channels that connected the cytoplasms of adja-
cent cells, it was years before their structure, shown in
Figure 14.21 [43]
, was determined
[44]
. Each channel in a gap junction is made up of 12 proteins called connexins. Six hexago-
nally arranged connexins are associated with each of the adjacent cell plasma membranes
that the gap junction spans. Each set of six connexins is called a connexon and forms half
of the gap junction channel. Therefore, one gap junction channel is composed of two aligned
connexons and 12 connexins. Each connexin has a diameter of ~7nm and the hollow center
formed between the six connexins, (the channel), is ~3nm in diameter. Gap junctions allow
adjacent cells to be in constant electrical and chemical communication with one another.
Of particular importance is the rapid transmission of small second messengers, such as
inositol triphosphate (IP
3
) and Ca
2
þ
.
It appears that all cells in the liver are interconnected through gap junctions. This presents
a possible dilemma. If even a single cell is damaged, deleterious effects may be rapidly
e
