25.4 : Assembly of Cytoskeletal Filaments

Cytoskeletal filaments are polymeric forms of smaller protein subunits. However, individual cytoskeletal filaments may easily disassemble or associate with other similar filaments to form rigid structures. Microfilaments, made of actin monomers, rely on actin-binding proteins to form bundles and create networks of individual actin filaments. Microtubules rely on microtubule-associated proteins (MAPs) to form sturdy cylindrical structures. However, the proteins involved in forming complex rope-like intermediate filament structures are still unknown.

Assembly of Actin bundles and Networks

Actin bundles can be classified into compact and loosely spaced bundles. Compact bundles consist of closely spaced parallel actin filaments, with their plus ends adjacent to the plasma membranes formed with the help of the actin-binding protein fimbrin, with two adjacent actin-binding domains to hold parallel filaments close together. Loosely spaced bundles known as contractile bundles rely on crosslinking actin-binding proteins such as α-actinin. α-actinin is a homodimeric protein, having a single actin-binding site that binds to two oppositely oriented actin filaments. Actin filaments can also form a network-like structure with the help of larger actin-binding proteins such as filamin. Filamin is a dimeric protein with an actin-binding domain and a dimerization domain at opposite ends of each subunit. This dimer is in V-shape, with actin-binding domains at the ends of each arm. Therefore, linking actin filament through these proteins form three-dimensional networks.

Assembly of Microtubule Cylinders

Microtubules are cylindrical assemblies of tubulin heterodimers that are several micrometers long and 25 nm wide. They are made up of 13 parallel protofilaments consisting of tubulin dimers arranged head to tail. MAPs such as Tumor Overexpressed Gene or TOG domain-containing microtubule polymerases aid in microtubule protofilaments assembly into cylindrical structures. Some of these TOG domains capture free tubulin, while others anchor the tubulin to the microtubule plus end, favoring the association of protofilaments and promoting microtubule assembly.