25.4:
Assembly of Cytoskeletal Filaments
The cytoskeleton comprises three types of protein filaments — microfilaments, microtubules, and intermediate filaments. These filaments assemble and disassemble according to the cell’s requirements.
Each type of filament is made up of smaller subunits that self-associate through end-to-end protein contacts and are held together by weak associations like non-covalent interactions and hydrophobic forces.
With the help of actin-binding proteins, microfilaments assemble either into bundles of individual filaments crosslinked into parallel arrays, or, as complex three-dimensional networks.
Microtubules consist of tubulin heterodimers that assemble end-to-end to form a hollow cylinder made up of thirteen protofilaments. Microtubule-associated proteins or MAPs help the protofilaments polymerize and stabilize the assembled structure.
Intermediate filaments are composed of elongated fibrous proteins that vary across cell types. These protein subunits form tetramers through a multistep process. Finally, the tetramers associate to form a rigid rope-like structure.
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.
Suggested Reading
- Foster, P.J., Fürthauer, S., Shelley, M.J. and Needleman, D.J., 2019. From cytoskeletal assemblies to living materials. Current opinion in cell biology, 56, pp.109-114. https://doi.org/10.1016/j.ceb.2018.10.010
- Rivas, G., Vogel, S.K. and Schwille, P., 2014. Reconstitution of cytoskeletal protein assemblies for large-scale membrane transformation. Current opinion in chemical biology, 22, pp.18-26. https://doi.org/10.1016/j.cbpa.2014.07.018