Category Archives: Desmosomal mitochondrial associations

Desmosomes in alveolar type II cells: perhaps not? or if so, not very many!

Desmosomal mitochondrial associations, Electron microgaphs of lung

While perusing hundreds of electron micrographs of alveolar type II cells in half a dozen species i was disappointed NOT to see any desmosomes, or if I saw them they were not very well developed and tangentially cut, but I really think they may exist in a different form than they do, at least, in liver.

This I surmise from the fact that very little of the alveolar type II cell is actually “tethered” to other cells. A large portion (basal plasmalemma) abuts basement membrane, a tiny bit is close to alveolar type I cells, that connection by the way is very thin and would not even provide enough space wherein a mitochondria could reside and be found tethered to a desmosome, if i could find a desmosome. The large (perhaps the largest) plasmalemmal surface is in the alveolar space and no desmosomes possible there.  So the hunt for desmosomal mitochondrial tethers in alveolar type II cells just came up empty. Empty for desmosomes, empty for desmosomal mitochondrial tethers, but of course there are plenty of mitochondria per se…. just not tethered to anything resembling a desmosome.  I don’t even have an image of something which might be considered “close”.

It makes sense in terms of physiology however not to have rigid structures tightly binging alveolar type II cells together…. the tremendous movement within the alveolus durin inspiration and expiration would make it a little untenable to have to use energy, move mitochondria, make and break associations within the cell and the intermediate filaments, and lose the intercellular bonds in the cadherin molecules 20 or 30 times a minute. (and remember that is slow compared to the inspiration and expiration of some animals).  So peripheral lung was probably a silly tissue to hunt for desmosomal mitochondrial tethers (there are other junctional complexes of course to prevent fluid from coming into the intercellular space that are easily seen, tight junctions and adherens junctions. Some describers of peripheral lung epi dont even mention desmosomes. HERE (i have never heard of this journal, so reader beware)

What element brings together intermediate filaments, mitochondria and desmosomes?

Desmosomal mitochondrial associations

What element brings together intermediate filaments, mitochondria and desmosomes? I think it would be nice to know which of these organelles is responsible for initiating the association of the three to create the desmosomal mitochondria tether which is connected via intermediate filaments. Which?
1) Intermediate filaments can “tug” on mitochondrial shape (morphology). This is clearly evident in countless micrographs.
2) Intermediate filaments bind with the desmoplakin protein (part of the desmosome) and the latter bonds with the dense portion of the desmosome (plakophilin, plakoglobin) just adjacent to the plasmalemma (on the intracellular side) and the intracellular ends of desmocolin and desmoglein (the main proteins in the intercellular space).
3) Mitochondria as calcium buffers may have be important in regulating the calcium dependent adhesion molecules, desmocolin and desmoglein, in particular formation and reduction of desmosomes. This is a function seen in other intermediate filament mitochondria tethers as well.
4) Mitochondria provide energy as ATP.
5) Also, the flattened part of the mitochondrial membrane which is adjacent to the desmosomal – mitochondrial tether area with intermediate filaments would probably include mitochondrial membrane anchoring receptors.
6) If what is reported is true (longer mitochondria produce more energy) then those long three or four thered areas on a single mitochondria would be “really active” in terms of energy production). Arrowheads = des – mit tethers; tj = tight junction; bar = 100nm; RER along the top right of the image. Syrian hamster hepatocyte.
A LIST OF VARIOUS accepted functions for membrane-mitochondria-filament associations
a- apoptosis
b- lipid transport
c- autophagy
d- mitochondrial morphology
e- intercellular junctions
So this is a obviously going to be the short list…. thee will be many more functions to come.

Desmosomal-mitochondrial tethers: x2

Desmosomal mitochondrial associations, Electron micrographs of liver, The cell: images, Ultimate order, the cell

Here is a gallery sheet of desmosomal mitochondrial tethers, and some are double, some are double-doubles (haha) and some have three tethers.  I can’t overemphasize how interesting these little structures are and how critical they must be for cell function. Just considering how the desmosome itself has become a known mechanism of cell signaling, then the energy provided (mitochondria) and the movement of proteins and mitochondria and signaling proteins via the intermediate filaments, and the latter involved also in cell shape change…. makes these structures very very important.  This gallery (making the gallery itself) caused me great grief… ha ha.. my little desk top computer just didn’t want to handle composite images of over a gig.  Would that I had real equipment…  wonder of wonders.  Enjoy the image(s) of whatever these DES-MiTes  (desmosomal-mitochondrial-tethers)  will ultimately be called (dumber names exist in science).

34 pix, 43 desmosomes, at least 56 mitochondria, numerous species represented here (ferret, rat, guinea pig, stub tail monkey, rhesus monkey, maybe others, and all images are from hepatocyte-hepatocyte junctions)

desmosomal mitochondria tethers and double tethers in hepatocytes

 

Questions about desmosomes and mitochondrial junctions

Desmosomal mitochondrial associations, Mitochondria: electron microscopy, Ultimate order, the cell

Desmosomes:

(who names these proteins — desmosome..  desmo — and soma, that is the easy button, cadherins…  well calcium dependent adhering molecules, i guess thats ok, desmoglobins… not so good, plakophilin, maybe that should be desmoplakoglobofilin.. ha ha…  i guess too that the plaque, and plako…. go together, but there are two intracellular zones (apparently) of the desmosome…  inner (which is already confusing because to me, if the desomosome is the unit being described, then inner would be the closest plaque to the center of the desmosome, which is the central dense line in the intercellular space, but no…someone  named it “backwards” with the center of the CELL rather than the center of the DESMOSOME as the reference point, thus what is named the outer desmosomal plaque is actually “inner” with reference to the desmosome).  It is astounding how differently we all describe our world– and it adds a whole lot of confusion and difficulty to learning and understanding).

More or less facts:
1) electron dense disc like plaques (Stedman’s medical dictionary recommends the spelling “disc” for all medical uses) so I will use disc.
2) extracellular-intra-and-intercellular-cell-to-cell adhesion discs
3) prominent in epithelial cells
4) 0.2 to 0.5 microns in the flat dimension (depending likely on whether the edge of the disc is in the plane of section or the center
5) very likely different states of cell activity change the dimension and the number and the location of desmosomes as well as the number of mitochondria which are associated.
6) Only a small percent of mitochondria are associated with desmosomes, mainly because there are many mitochondria in each cell. (Volume vs perimeter consideration).

Desmosomal cadherins – desmocolin (3 isoforms) and desmoglein (4 or more isoforms). DSC2 and DSG2 are the most common.

Tying the desmosome to intercellular elements are the “intermediate filaments: a diverse class of flexible filaments that provide mechanical strength to cells. They make up hair, nail, horn, and scale cells, they form the nuclear lamina, which lies just inside the inner nuclear membrane, they span cells to provide strength to epithelial tissues, and they anchor organelles and stabilize the cytoplasm” with these data (Intermediate filaments 6–10 strands per filament (6 was quoted for those which are next to desmosomes), non-polar, outside diameter he quotes as ~10 nm (I think this might be larger, or maybe stains add dimensions)) an edited quote from Methods for modeling cytoskeletal and DNA filaments by Steven Andrews (Physical Biology, Volume 11, Number 1 )

Desmoglein 2

“Desmoglein-2 is a 122.2 kDa protein composed of 1118 amino acids. Desmoglein-2 is a calcium-binding transmembrane glycoprotein component of desmosomes in vertebrate cells. Currently, four desmoglein subfamily members have been identified and all are members of the cadherin cell adhesion molecule superfamily.”

Intermediate filaments – desmosomes – mitochondria

Desmosomal mitochondrial associations, Electron micrographs of liver, Mitochondria: electron microscopy, The cell: images, Ultimate order, the cell

I havn’t read much (or found much to read) about the making – breaking – moving – adjusting of desmosomes, or the energy requirement for desmosome modification, but it seems too much a coincidence that mitochondria would be closely tethered to desmosomes and not provide this function. That said, they have been photographed by me in mouse, rat, neonatal rat, ferret, hamster, syrian hamster, dog, and guinea pig, just to name a few in the list that I have looked at in the last weeks. And they are so similar in all, that so far, if i list one image of a desmosomal-mitochondrial junction from one species I cannot tell it from another. This is good, i guess, but it would be more interesting if the structure showed some variation in structure….. that could perhaps be correlated with differences in the component proteins.

Here is one desmosomal-mitochondrial junction from ferret, which didn’t have a nice even pattern of cadherins in the middle, but did have a punctuated central line…with dots less than 20nm apart…. they seemed a little staggered.  Here is the original micrograph (i removed a scratch in the negative not in the area of the desmosome using photoshop bandaid tool, but it otherwise just a scan of the print. 5940 18648 ferret hepatocyte.

The image below it is an enlargement of the box in top image. Ribosome-red dot for size, and the black lines overlie densities in the intercellular area of the desmosome.


Desmosome-to-mitochondria: connections

Desmosomal mitochondrial associations, Electron micrographs of liver, Mitochondria: electron microscopy, Rants, The cell: images, Ultimate order, the cell

More desmosomal mitochondria tethering from hamster hepatocytes. This particular view has two mitochondria, and one shows a line of “dots” or fibers or fibrils in cross section.

This image is from a syrian hamster hepatocyte, and it is just a routine TEM but I noticed (while making my gallery collection of desmosomal-mitochondrial images) that one of the mitochondria showed the repeating dots (cross sections likely of intermediate filaments (maybe types I and II).

Upper image is unretouched micrograph and lower image has been pseudocolored. The latter has green for the two mitochondria that are tethered to the desmosome  at their outer mitochondria membrane (which appears rigid where intermediate filaments are present, and a distinct and definitely separated inner mitochondrial membrane). Along with the intermediate filaments are connections to the desmoplakin molecules the latter being part of the outer dense plaque of the desmosome. The yellow is the cytoplasmic area of the two adjacent cells including the intercellular space and the spot desmosome. Red dot is appoximately the size of a ribosome (27nm) which makes these filaments cut in cross section about 13.5nm in diameter (orange dots in a row) bottom electron micrograph. This hastily made measurement is not that far off from the reported 10nm intermediate filament made up of four monomer filament tetramers (haha… figure that out).

According to Thomason et al,  desomosomal proteins are as follows (slightly rearranged to make more sense to me): Desmosomes have five major component proteins, the DCs (desmosomal cadherins) DSG (desmoglein) and DSC (desmocollin) –DSC and DSG are the desmosomal adhesion molecules. Plakin family cytolinker DP (desmoplakin), and the arm (armadillo) proteins PG (plakoglobin) and PKP (plakophilin).  DP links the desmosomal plaque to the IF (intermediate filament) cytoskeleton, and PG and PKP are adaptor proteins that link between the adhesion molecules and DP.

Who could guess that desmosomes know hebrew?

Desmosomal mitochondrial associations, Rants, Science and art cover illustrations, The cell: images, Ultimate order, the cell

Was looking at this model for the cadherins of a desmosome and I just happened to see “shin” there in reds and oranges. I love it when nature intersects civilization in an unexpected manner…. so fun, ha ha.  Just out of deference to the authors of this paper on desmosomes, 3D and electron microscopy I will list their reference in case you want to actually see the original. Al-Amoudi, et al., Nature05994 (2007)

More on desmosome shape

Desmosomal mitochondrial associations, Electron micrographs of liver, The cell: images, Ultimate order, the cell

“Desmosomes are a complex assembly of protein molecules that form at the cell surface and mediate cell–cell adhesion. Much is known about the composition of desmosomes and there is an established consensus for the location of and interactions between constituent proteins within the assembly. Furthermore, X-ray crystallography has determined atomic structures of isolated domains from several constituent proteins. Nevertheless, there is a lack of understanding about the architecture of the intact assembly and the physical principles behind the adhesive strength of desmosomes therefore remain vague. We have used electron tomography to address this problem. In previous work, we investigated the in situ structure of desmosomes from newborn mouse skin preserved by freeze-substitution and imaged in resin-embedded thin sections. In our present work, we have isolated desmosomes from cow snout and imaged them in the frozen unstained state. Although not definitive, the resulting images provide support for the irregular groupings of cadherin molecules seen previously in mouse skin.” ABSTRACT from Gethin Rh. Owen, Devrim Acehan, K.D. Derr, William J. Rice, David L. Stokes . Some things might be right, others not…. the last idea that cadherin molecules are grouped irregularly i don’t like. (This article i wont read as it is pay-per-view, which really galls me particularly because most research is paid for by tax-dollars and should be free).

” I found a dimension for the width “wide intercellular space (~240 A)” at 24nm and a measurement of the intermediate filament at 8nm (i presume diameter). The 22-24nm (could be less in some instances more like 15nm) as the width of the desmosomal intercellular space (which includes the densities on the outer leaflet of the plasmalemma from both cells and the central dense line of the desmosome.  That measurement looks about right. From this I estimate the width of the electron lucent annulus of the desmosome (which is much more evident when there is a tight junction on either side of the desmosome) to be dependent upon where the section sectioned the spot desmosome, and whether the cut was equatorial or tangent to the spot itself. On one micrograph (stub tail monkey hepatocyte) in which one area of the desmosome is close to a tight junction, shows this lucent area (the outer annulus) to be about 35nm in its radius – that dimension applies to the edge of the central dense line extending to the tight junction. The width of that particular desmosome (where the central line was apparent) was @265nm.  This makes the ratio of the dense desmosomal central line density distance to lucent annulus distance in cross section about 3.5%.

That lucent area may not be a uniform annulus, but if it were even, this assumes pretty much a “round” desmosomal spot weld. In measuring the radius of the annulus (just in the part ring part) I understand that the central dense line of the desmosome will appear in any view with the spot perpendicular to the plane of section, and this doesn’t diminish the fact that closer cuts to the outer edge of the desmosome will have a greater annulus to spot ratio. Fuzzing of the central dense line in the desmosome occurs when the angle of the section is not perpendicular to the spot, and can happen either at an equatorial section or anywere past that equator. So. any question I can ask, someone has an answer to…. so here is the definition of calculating the area of an annulus.. ha ha “An annulus (Latin word for ring) is a two-dimensional region of space bounded by two concentric circles. The area of an annulus is the difference in the areas of the larger circle of radius R, and the smaller circle of radius r. Mean radius (ρ) is the average of the exterior (R) and interior (r) radii. Breadth (δ) is the width of the annulus. “ So I just have to figure out how to use the online calculator.

The ratio of lucent annulus to dense desmosome is not too apparent when there is no tight junction visible right next to it. But that said, I can see a slight increase in plasmalemmal density for a short distance (same type of annulus arrangement as if there were a tight junction there) on each end of the desomosome cross section.

Begin here: “empty annulus” outer ring around the desmosomal protein core”

Desmosomal mitochondrial associations, Electron micrographs of liver, The cell: images, Ultimate order, the cell

How funny this is, the perimeter of a desmosome with this very precise and quite abrupt “beginning”. It seems that adjacent cells (with a concentric area of pretty well adhered plasmalemmae (two adjacent cells involved)) make the abrupt 45 degree bend just to (coincident with?)  the widened intercellular space at the core of the desmosome to its typical width of about 25nm (up from the space between two cells at its closest… more around 17nm).

What is most interesting is what signals the 45 degree spread (bend) on the plasmalemma just before the desmosomal disk, and why is it so electron lucent? or free or proteins?.  This is a “free” zone before the electron dense desmosomal complex proteins that make their junctional adherent  weld of about 150nm. the width of the annulus. The area of the annulus would vary depending upon where in the spot desmosome the section happened to fall, and a cut in the annulus completely would just look like a wider two-cell junction, showing no desmosome at all.  Whether the width of the annulus around the desmosome is consistent from one species, or even one cell type to another is likely not known.  I will google to see.