Chapter 9: Nucleus & Control of Gene Expression

Nucleus & Control of Gene Expression structures fulfill critical roles, including providing structural support, determining cell shape, organizing internal organelles, serving as tracks for intracellular transport, acting as the force-generating apparatus for motility, and driving cell division. Microtubules are hollow, rigid, and highly polarized filaments assembled from αβ-tubulin heterodimers, with growth and shrinkage governed by GTP hydrolysis and regulated by Microtubule-Associated Proteins (MAPs). The inherent switching between phases of growth and rapid shortening is known as dynamic instability. MTs originate from Microtubule-Organizing Centers (MTOCs) like the centrosome, where the γ-tubulin ring complex (γ-TuRC) nucleates new structures and dictates their polarity. Motor proteins specific to MTs include Kinesins, which primarily facilitate anterograde transport (towards the plus end, away from the cell center), and Cytoplasmic Dynein, which mediates retrograde transport (towards the minus end, toward the cell center). Organized MTs form the characteristic 9 + 2 array of the axoneme found in motile cilia and flagella, whose bending movement is powered by axonemal dynein arms sliding adjacent microtubular doublets relative to one another. Defects in these structures are linked to various ciliopathies, such as polycystic kidney disease (PKD). Intermediate filaments are tough, non-polarized, ropelike structures that confer mechanical strength to tissues, demonstrated by keratins in epithelial cells, the failure of which can cause blistering diseases like epidermolysis bullosa simplex (EBS). Actin filaments are flexible, polar structures involved in motility and contractility. Cell movement relies heavily on the controlled assembly of branched AF networks at the leading edge (lamellipodium), a process stimulated by the Arp2/3 complex and various specialized actin-binding proteins (ABPs), including profilin and cofilin. The force to pull the cell body forward is generated by conventional Myosin II motors interacting with AFs behind the leading edge. Myosins also drive muscle contraction within the highly organized sarcomere structure, where the sliding filament model, regulated by calcium and the troponin-tropomyosin complex, explains how filaments slide past each other to shorten the muscle. Unconventional myosins, such as the processive Myosin V, function as motors for localized organelle transport. Specialized cytoskeletal toxins, like colchicine (MT inhibitor) and phalloidin (AF stabilizer), have been instrumental in studying these dynamic processes. Importantly, many fundamental cytoskeletal mechanisms, such as those related to division (FtsZ) and segregation (ParM), have corresponding structural and functional protein homologs in prokaryotic cells.