Since these “Inner Life of the Cell” posts appear to be popular with high school students studying for their exams and serving as fodder for youtube debates about evolution, I’m going to break with my tradition of only posting in November and finish up these series of posts. So back to it:
When we last left our leukocyte he had just had been stimulated to provide an inflammation response. While I’m grouping this part of the explanation under “Adhesion”, most of the adhesion part of this video was covered previously in “Rolling”. This section deals more with the basic organization of the cell, and the transmission of the adhesion signal. Both of these will be important in activation, but in the interests of matching with the explanation video I’ve just lumped it in with “Adhesion”. With that caveat, let’s return to the video and our recently stimulated leukocyte.
0:31-0:37: We’re know crossing from the outer (or “top”) layer of the leukocyte membrane (the part that has adhered to the endothelial cell) and delving inside it. We’re still at the membrane but we’re now in the inner part which is an entirely different environment. Whereas the top or outer part of the membrane was important in contacting the skin cell, the inner portion is dedicated to transmitting the fact that the cells have “docked”. Here’s what the video says:
The inner leaflet of the bilayer has a very different composition than that of the outer leaflet. While some proteins traverse the membrane, others are either anchored into the inner leaflet by covalently attached fatty acid chains, or are recruited through non covalent interactions with membrane proteins. The membrane bound protein complexes are critical for transmission of signals across the plasma membrane.
Basically, there are some proteins that stick through the membrane (like a straw through the peel of an orange) while others are just stuck to the inside (i.e. attached to the underside of the orange peel but not visible from outside) by “fatty acid chains”, and lastly there are things that are stuck to these anchored pieces, but aren’t anchored themselves (like if your friend was holding onto the edge of a cliff and you were holding onto him). All these proteins are important in conveying messages from the surface to the interior of the cell (in this case “Hey, we’ve adhered to an inflammation site”).
0:38-0:42: We’re now going deeper into the white blood cell, leaving the membrane (the outermost part) and entering the cystol, the gooey interior of the leukocyte. A structure known as the cytoskeleton, comprised of spectrin tetramers (spectrin is a protein, and tetramer means that four of them come together to form a functional unit) is attached at several anchor points to the membrane proteins and holds the cell together and keeps it organized (so that everything doesn’t just mix together).
Beneath the lipid bilayer, spectrin tetramers arranged into a hexagonal network are anchored by membrane proteins. This network forms the membrane skeleton that contributes to membrane stability and membrane protein distribution. The cytoskeleton is comprised of networks of filamentous proteins that are responsible for the special organization of cytosolic components.
0:43-0:52: Now we’re delving even deeper and looking at actin filaments. Actin is one of the most abundant proteins in the cell and forms these long filaments which will constitute an important part of the cytoskeleton. Whereas spectrin provides a basic structure to the cystoskeleton, actin will be more important in cytoskeleton dynamics and will thus be instrumental in helping convey signals (such as the “Hey we’ve adhered” message) around the cell.
Inside microvillae, actin filaments form tight parallel bundles which are stabilized by cross-linking proteins. While (deeper?) in the cystol the actin network adopts a gel-like structure, stabilized by a variety of actin binding proteins.
0:53-1:01: Remember how I was saying actin was important in dynamics? Well, here you can witness it yourself. These long filaments are continuously forming and coming apart allowing the cell to convey information to all its parts. Note that these filaments have a directionality – they only grow in one direction and are capped at the other end.
Filaments, capped at their minus ends by a protein complex, grow away from the plasma membrane by the addition of actin monomers to their plus end. The actin network is a very dynamic structure with a continuous directional polymerization and disassembly.
1:02-1:07: Here we see regulation of the actin network by other proteins. Filaments can be cut in order to cause them to come apart or to regrow to other parts of the cell. Cofilin is an example of one of these kinds of actin regulating proteins.
Severing proteins induce kinks in the filament and lead to short fragments that rapidly depolymerize or give rise to new filaments.
1:08-1:15: Ok now we leave actin and come to microtubules:
The cytoskeleton includes a network of microtubules created by the lateral association of protofilaments formed by the polymerization of tubulin dimers. While the plus ends of some microtubules extend toward the plasma membrane, proteins stabilize the curved conformation of protofilaments from other microtubules, causing their rapid plus end depolymerization.
Microtubules are created by the joining together of proteins called tubulin (dimer means that two tubulins are a single functional unit in contrast to the actin tetramer (4 molecules = 1 functional unit)). Much like actin they have directionality, they rapidly polymerize and depolymerize as needed and serve as “tracks” on which certain proteins can travel. The term protofilament just means a short microtubule that can grow into a full filament.
1:16-1:26: Next up is kinesin, which seems to have become the star of this video. Kinesins are motor proteins that travel along microtubules carrying important cargo. In this case, the kinesin is carrying a vesicle, which is essentially a bubble full of proteins and other important molecules that are needed at other parts of the cell. This is a routine function in the cell, and not necessarily specific to the inflammation response.
Microtubules provide tracks along which membrane bound vesicles travel to and from the plasma membrane. The directional movement of these cargo vesicles is due to a family of motor proteins linking vesicles and microtubules.
1:27-1:34: As we watch the little kinesin dragging his vesicle we zoom out and see some of the larger functional units of the cell. Normally proteins and other important molecules diffuse to their correct location, but in some cases diffusion is insufficient (i.e. the molecule is too large) and these motor proteins have to drag them to the correct spot. Up in the right corner you see a mitchondria, often referred to as the power plant of the cell (it’s important in making energy for the cell), an example of a structure that would require transport by kinesin. The large glob dominating the center is the centrosome from which all the microtubules originate.
Membrane bound organelles like mitochondria are loosely trapped by the cytoskeleton. Mitochondria change shape continuously and their orientation is partly dictated by their interaction with microtubules. All the microtubules originate from the centrosome, a discrete fibrous structure containing two orthogonal centrioles and located near the cell nucleus.
Ok so we’ve seen how the cell can communicate messages from the surface to the nucleus and gotten a basic idea of its organization, but how does it respond appropriately to the inflammation signal? We’ll look at that in the next post “Activation”.
