Cytoskeleton Gestalt

In this day, some biologist have to move beyond the simplistic view that the cell is a bag of M&Ms. What do I mean by that? It's the idea that enzymes and organelles are free floating entities within the cell.

On the other hand, don't tell me that the cytoskeleton provides a static skeleton that fixes each cellular component.

The cytoskeleton is a dynamic and sensitive cellular organizer that constantly reshapes itself in response to extra-cellular clues. And those M&Ms aren't nailed to some part of the cytoskeleton. No, in fact they are moved around and dynamically organized by microtubules, actin and the other cytoskeletal filaments.

Which brings me to another subject ... how many cytoskeletal networks are there?

There are quite a few. And so in that vein here is a pictorial view of the cytoskeleton:

Actin. It's the main muscle of the cell. Through associated motors (myosin) or simply by polymerizing, actin moves organelles and enzymes over short distances. Actin also pushes and pulls on the cell's outer membrane giving the cell it's basic shape. And those actin filaments love to contract. The actin meshwork is also connected to the cell's attachments to the extracellular environment and drives cellular locomotion. In animal cells (and most protozoa) actin is used to form the cytokinetic furrow, the contraction that separates two halves of a dividing cell. Actin is everywhere (and the dirty secret that you're not suppose to know, it's in the nucleus too.)

Microtubules. These long tubes are both the highways and brains of the cell. Because microtubules are so long and because the plus ends are usually pointed towards the periphery and the minus ends are pointed towards the center of the cell, microtubules can differentiate these two cellular zones. Want to send things to the middle of the cell? Jump on the nearest microtubule and go towards the minus end. This is handy if you want to get to the nucleus which is located right where all the minus ends converge. Want to go to the periphery? Go towards the plus end. So as oppose to actin which is used for short distance transport, microtubules are the preferred track for long distance transport.

The cell labels certain microtubules that are pointed towards "special" peripheral zones such as the leading edge. In the micrograph on the right the labeled microtubules are green/yellow while the unlabeled microtubules are red. Thus if you are at the center of the cell and need to go to where all the action is happening, you hitch a ride on the labelled microtubules.

But that's not all.

Microtubules can control how the cell is shaped by orchestrating actin dynamics. You see if actin is the muscle, microtubules are the brain. How is this done? There is some intimate link between microtubules and the rho family of G-proteins, these molecules are the main regulators of actin polymerization, contraction and disassembly. Much is yet to be learned about how this elaborate feedback system works, but most of cellular morphogenesis involves this interplay between microtubules and actin.

Despite all these wonderful activities in "higher eukaryotes", in budding yeast microtubules are mainly responsible for moving DNA around. In budding yeast, microtubules move the nucleus towards the newly formed bud and then into the neck connecting the mother and bud. As the cell cycle progresses to mitosis microtubules are responsible for pulling the sister chromosomes apart and segregating them into the two daughter cells..

Just to remind you what mitosis looks like, here's a video. While you watch it think of how the microtubules are moving the chromosomes around while actin is determining the general shape of the cell (including the final cleavage aka cytokinesis):

In the realm beyond actin and microtubules less is known. Here are the other cytoskeletal filaments:

Intermediate filaments. These come in all sorts of varieties. Vimentin (micrograph on the right), neural filaments, keratin. One related member is the lamins, the intermediate filaments that line the inside of the nuclear membrane (micrograph below on the left). Intermediate filaments are thought to play mostly a structural role, but as I noted above, not much is known.

A setback in the intermediate filament field was the vimentin knockout mouse. This animal had only minor problems ... a surprise considering that vimentin is the main cytoplasmic intermediate filament in most cells (in fact some cells in the knockout mouse had no cytoplasmic intermediate filaments!) Knockout mice lacking certain keratins show skin blistering and other problems related to cellular stress. I must add that there are MANY keratin genes and these are mostly found in the skin. Neurofilaments are thought to be structural components that help neurons retain their shape. I'm not sure on what is the latest from that field. Mutations in lamins lead to many types of muscular dystrophies and premature aging. It is thought that lamins help nuclei to cope with physical stress.

Spectrin. This meshwork is mostly forgotten by most biologists but it's everywhere. It lines the outside of the golgi and other organelles and in many cells, it sits under the plasma membrane.

Septins. This class of cytoskeletal filaments have been generating a lot of interest recently. They act to close membranes, like dynamin except that septins sit on the inside of a constriction while dynamins sit on the outside. But that's not all that septins do. They also limit the flow of particles across the constriction, so they're like a sieve. Septins are found at the cytokinetic furrows, that is the last connection between two dividing cells. In budding yeast, septins can help to limit the flow of molecules from the bud to the mother and vice versa. In fact on the right is an image of a budding yeast with its septin ring. Septins thus contribute to the differentiation between the two daughter cells.

OK that's all for now. Till then remember, the cytoskeleton is your friend! (Man that was corny)