Cytoskeleton I: Actin filaments and associated proteins

Cytoskeleton I.
Actin Filaments and Associated Proteins I want to touch briefly on the cytoskeleton, the array of filaments in the cytosol that not only helps to give shape to cells, especially animal cells that have no cell wall around them, but that also serves a kind of railroad track for the cell upon which it can move around organelles such as mitochondria, some kinds of vesicles and such.
The name cytoskeleton--cell skeleton--suggests the ideas that this network comprises a kind of permanent structure for the cell. For some cell structures this is true. For example in neurons, i.e., nerve cells that have long axons and that never divide, the axon contains a pretty much permanent array of filaments--actin filaments, intermediate filaments called neurofilaments and microtubules--that run along the main axis of the axon. These are used to carry synaptic vesicles, mitochondria and plasma membrane components to the end of the axon--the synaptic terminal, and they are also used to ferry materials from the nerve terminal back to the cell body for degradation or recycling.
However, most cells do not have a fixed shape like neurons and they must respond to a diversity of signals which requires their being able to change shape or even undergo cell division. A permanent structure would be a disadvantage and thus the cytoskeleton of most animal cells is very dynamic--that is, its various components can form or disintegrate in response to conditions. Perhaps the most dramatic example of this is that of the mitotic spindle, an array of microtubules that forms during mitosis that is responsible for the separation of pairs of chromosomes into the two daughter cells. These microtubules form at the beginning of mitosis and disappear at the end of mitosis. Thus they are extremely transient, but they're also essential for the proper apportionment of genetic material into the daughter cells. Cells can move around within the organism, especially during development, or they can crawl around on petri dishes in tissue culture. These amoeboid movements appear to be driven by the formation and breakdown of force generating structures in the cell that require actin filaments. In short many cellular processes require the dynamic formation and disintegration of long cellular filaments, while some require more or less permanent arrays of cytoskeleton. What determines the formation, stability or disassembly of these cytoskeletal elements is an area of active interest.
As you probably know there are three different kinds of cytoskeletal structures; each is made up of polymers of protein and each class is made of different kinds of proteins. The smallest used to be called microfilaments, but because it is now known that they are made up solely of polymers of actin, they are now called actin filaments. Actin is a globular protein that under some conditions in the cell can be induced to polymerize end to end. When this happens the actin monomers bind in two long strands that wrap around each other in a long helical structure that is called filamentous actin: (Figs. 18-11 a; 18-2). The monomers are held together by non-covalent bonds, so of course, this process is reversible and the filaments can dissociate into monomers as well. Whether the actin is primarily in the globular or filamentous form is partly controlled by the concentration of monomers (see Fig. 18-12), and partly by other proteins (see below). An actin filament has a directionality or polarity; that is, the ends are slightly different and can be distinguished biochemically; one end is called the minus end, the other one is the plus end. While G actin monomers can be added at either end of a filament, they accrue more rapidly at the + end, so that filaments grow faster in the plus direction. (Lodish et al. indicate what the difference between plus and minus is in terms of the actin structure, and I'll let you find it there).
Actin is probably the most important of the cytoskeletal elements in determining cell shape, and it has many functions in movement as well. These functions of actin filaments are mediated by several different classes of proteins--myosins, cross-linking proteins, membrane microfilament binding proteins, and actin stabilizing and destabilizing proteins. The primary proteins responsible for cell shape are those that cross-link actin filaments (Fig 18-5 and Table 18-1), and those that link the actin to membrane proteins (e.g., Figs. 18-7 and 18-9). The cross-linking proteins add rigidity to the cytoskeleton as cross-braces in a building or on shelving do. The membrane-linking proteins attach the membrane of the cell to the cytoskeleton, which allows for changing the shape of the cell as the cytoskeleton contracts or rearranges.
Actin filaments are stabilized by interaction with proteins such as the capping and profilin while monomers are stabilized by interaction with thymosin b 4, and filaments can be disrupted by proteins such as gelsolin. A great deal of study has gone into sorting out the nature and degree that each of these interactions has on the stability of actin filaments, some of which is covered in Lodish et al. I only ask that you understand that actin filaments are important cytoskeletal elements, that they are formed by polymerization of G actin monomers, and that many other proteins interact with actin to regulate the stability and rigidity of the actin filaments.
As you probably know, permanent filaments of actin in muscle cells are necessary for muscle contraction. In muscle these myosin and actin structures are fixed and permanent. However, it is now known that motility or movement in many other kinds of cells is also driven by actin/myosin systems. The difference is that the actin filaments can assemble and disassemble in response to the cell's environment, and that there are different kinds of myosin in different kinds of cells. That is, actin seems to be the same everywhere in the organism--there's probably only one gene or some closely related genes that encode actin proteins, but there is a large family of related by different genes that encode for myosin molecules that can use actin to drag themselves along.
All known myosin types have a similar structure, consisting of a "head" group that can bind to actin filaments, and a tail that enables the myosin to bind to some other cellular structure (including, sometimes, other myosin molecules). In all cases studied the myosin head binds to the actin filament and uses the energy from ATP hydrolysis to "walk along" the filament. The other tail end of the myosin latches onto something, such as a vesicle, and drags this cargo along with it. The best studied myosins are myosins I, II and V (Roman numerals, here, and sometimes subtypes called Ia, Ib, etc.) Myosin II is the one that's used in skeletal muscle. Myosins I and V seem to be important in the movement of some kinds of vesicles within cells. Myosin/actin interactions are also responsible for the contraction of the "contractile ring", a structure that forms around the middle of a dividing cell that contributes to cytokinesis, the process by which the two halves of a mitotic cell divide. The mechanism of myosin movement is best worked out for myosin II in skeletal muscle, but is thought to be similar in all types of myosin--see the model in Fig. 18-25 and accompanying movie. Because myosin uses the energy from ATP hydrolysis to propel the movement of many cellular organelles and other structures, it is often referred to as a "motor protein".