Biology Reference
In-Depth Information
Standard College Dictionary defines the term domain as 'a territory over which dominance is
exerted'. In proteins, domains are a component of the total protein structure and they exist
and function essentially independently of the rest of the protein. Many proteins consist of
several functional domains that can be very large, varying in length between 25 to 500 amino
acids. Among the various types of protein domains are those that bind to specific portions of
a nucleic acid that are also referred to as a domain. So the term domain can refer to functional
patches of proteins, nucleic acids or, as we will see, membranes!
Quite different from protein and nucleic acid domains are domains that comprise
membrane structure. It is universally accepted that biological membranes are not homoge-
neous mixtures of lipid and protein but instead consist of patches of widely differing and
often rapidly changing composition called domains. Domains exist in a bewildering array
of sizes, stabilities, lipid and protein compositions, and functionalities. Membrane domains
can be roughly divided into large, stable macrodomains and small unstable lipid microdo-
mains. Most macrodomains are stable for extended time periods and so are isolatable and
fairly well defined. The major part of most biological membranes, however, is likely
composed of an enormous number of poorly understood and less stable lipid microdomains
that are difficult to study, and so far impossible to isolate in pure form. Through the years the
reputed size and stability of lipid microdomains has continuously decreased from microns
down to tens of molecules or so with associated lifetimes into the un-biological nanosecond
range
[24]
. While large macrodomains are easily imaged, their analogous lipid microdomain
counterparts in biological membranes are more elusive, far smaller, and thus harder to image.
In the following sections, examples of macroscopic and lipid microdomain imaging are
presented.
Membrane Macrodomains
Most macrodomains owe their discovery to the development of electron microscopy in the
1940s and 1950s. Some examples including basolateral and apical halves of epithelial cells,
thylakoid grana and stroma, sperm head and tail, tight junctions and bacteriorhodopsin
2-D patches in the purple membrane of Halobacterium halobium have been known for decades
and will not be considered here. Images of the macroscopic domains; gap junctions, clathrin-
coated pits, and caveolae will be briefly discussed.
Gap Junctions
Gap junctions were probably first observed by the pioneering electron microscopist J.D.
Robertson in 1953
[25]
. Robertson's 'Unit Membrane' model was based on his many EM
images. Gap junctions were eventually characterized in the late 1950s and early 1960s by
several investigators including George Palade and his wife Marilyn Farquahr in 1963
[26]
.
Gap junctions are tube-like structures that connect the cytoplasms of adjacent cells
[27,28]
.
Unlike tight junctions that press adjacent cells together, gap junctions maintain a 2 to 3 nm
spatial gap between cells. Their function is to allow for rapid communication between cells
through exchange of various small molecules (~1,000 molecular weight limit) and ions.
Important examples of gap junction-transported solutes include the second messengers
cAMP, IP
3
, and Ca
2
รพ
. Cells with gap junctions are therefore in direct electrical and chemical
contact with each other
[29]
. Gap junction intercellular connections are through hollow cylin-
ders called connexons. Each connexon is a circular arrangement of six subunits of a protein
