Question

Compare and contrast the polymerization of actin and tubulin in vitro and in vivo.

Answer 1

Intermediate filaments are made up of smaller subunits that are themselves elongated and fibrous, whereas actin filaments and microtubules are made of subunits that are compact and globular—actin subunits for actin filaments, tubulin subunits for microtubules.

All three types of cytoskeletal filaments form as helical assemblies of subunits which self-associate, using a combination of end-to-end and side-to-side protein contacts.

The three types of cytoskeletal polymers are held together by weak noncovalent interactions, which means that their assembly and disassembly can occur rapidly, without covalent bonds being formed or broken.

Within the cell, hundreds of different cytoskeleton-associated accessory proteins regulate the spatial distribution and the dynamic behavior of the filaments. Acting together, the accessory proteins enable a eucaryotic cell to maintain a highly organized but flexible internal structure and, in many cases, to move.

Through its ability to form helical polar rods by polymerization, actin constitutes a versatile building unit for both pushing and pulling (in concert with myosin).

The starting point for actin filament assembly is the formation of a nucleus of three actin monomers, which is considered to constitute the rate-limiting step in vitro and in vivo. Once actin filaments are nucleated, other accessory proteins are thought to take over and promote their elongation at their fast-growing ends. Whether this is accomplished by the nucleator or another factor depends on the mechanism of nucleation. Due to head to tail assembly of actin monomers, actin filaments are intrinsically polar, harboring a fastgrowing, barbed and a slowly growing, pointed end. The differential critical concentrations of polymerization at the two ends can cause net flow of actin monomers through the filament in a process known as treadmilling also operating in cellular structures like the lamellipodium.

In addition, filament ends and sides are subject to regulation by uncountable filament binding factors with numerous activities. These include e.g. capping, stopping and protecting ends from growth and depolymerization..etc. It is commonly agreed that a composite of all these activities drives the turnover of a complex structure such as the lamellipodium.

Nevertheless, it is also clear that the essential prerequisite of formation and maintenance of a given actin structure, lamellipodium or smallish actin accumulation accompanying endocytosis, constitutes the nucleation event, and an impressive progress has recently been made in the discovery of mechanisms and factors catalyzing this important process.