In Chapters 17 and 18, we have seen how microfilaments, microtubules, and intermediate filaments provide structure and organization to cells. Without this elaborate system, cells would lack all order and hence all possibility of function or division. The name cytoskeleton suggests a relatively static structure on which the cell organization is hung. However, the cytoskeleton is actually a dynamic framework responding to signal transduction pathways and operating both locally and globally to provide cells with order to undertake their functions.

In outline, we have elucidated many of the distinct and common functions of the three filament systems. We know most of the components and probably all the motors. However, in many ways, this is just an exciting beginning. With the available sequenced genomes and, at least in principle, a complete inventory of the cytoskeletal components, we have a parts list. However, a parts list is just that; what we need is to understand how the parts come together in specific processes.

A very active area of research today is the use of the parts list to systematically identify the locations (through GFP fusions), functions (through RNAi knockdown and CRISPR/Cas9 knockouts), and associated partners (through isolation of protein complexes) of all cytoskeletal components. Consider that there are about 45 genes in animals that encode members of the kinesin superfamily, yet we know what only a small subset of those proteins do or what cargoes they carry, and for what purpose. In each case, it is reasonable to assume that the motors are regulated, but very little is currently known about how. It will be important to understand how motors pick up the right cargo and then dissociate from it when they arrive at their destination. As we begin to put all the pieces in place, it will be increasingly possible to reconstitute specific processes in vitro. Some aspects of the mitotic spindle have already been reconstituted, which is an encouraging beginning, but it will be some time before it is possible to reconstitute the whole process.

Structural biology will play a major role in this research because it will allow us to see in detail how different components of the cytoskeleton work. Consider the large number of proteins that associate with the microtubule (+) end—the so-called +TIPs. We know a bit about how they maintain their associations with the microtubule end, and recent work has suggested that these associations can change in different parts of the cell—again, we are only just beginning to see how these processes are regulated.

Perhaps the biggest—and most exciting—challenge is to uncover how signal transduction pathways coordinate the functions of all the different cytoskeletal elements within single cells, and in different cellular contexts. How cells organize and regulate different processes in various regions within a single cell is a question that is only now beginning to be tackled. We are beginning to see glimpses of what is in store from the signal transduction pathways that regulate cell polarity and allow cell migration.

Although all these studies are likely to be aimed at basic cell biology, such studies, as we can see from the studies of intraflagellar transport and intermediate filaments, often open a window into the underlying basis of disease, from which strategies for treatments can be developed. The interplay between basic cell biology and medicine contributes immensely to the excitement and social value of working in this area.