Intracellular transport machinery

The intracellular transport machinery is a complex network of cytoskeletal filaments, molecular motors, and regulatory proteins that facilitate the spatial organization and movement of cellular components [1]. This system primarily utilizes microtubules and actin filaments as structural tracks, along with motor proteins such as kinesins, dyneins, and myosins that convert chemical energy into mechanical work to transport organelles, proteins, and mRNA [2]. Additionally, the machinery includes the nuclear pore complex and transport receptors, such as exportins (e.g., XPO1), which regulate the translocation of molecules between the nucleus and cytoplasm [3]. Dysregulation of these transport processes is a hallmark of various pathologies; for instance, cancer cells often hijack this machinery to support rapid mitosis or to export tumor suppressors from the nucleus [4]. Therapeutic strategies targeting this system include microtubule-stabilizing or destabilizing agents and selective inhibitors of nuclear export (SINE) [5]. However, because these processes are fundamental to all eukaryotic cells, pharmacological intervention often results in significant toxicities, most notably peripheral neuropathy due to the disruption of long-distance axonal transport in neurons [6]. (Sources: [1] Alberts B, et al. Molecular Biology of the Cell; [2] Hirokawa N, et al. Nat Rev Mol Cell Biol. 2009; [3] Kim J, et al. J Hematol Oncol. 2018; [4] Millecamps S, et al. Nat Rev Neurol. 2013; [5] Jordan MA, et al. Nat Rev Cancer. 2004; [6] Argyriou AA, et al. Crit Rev Oncol Hematol. 2012).

Other names

Intracellular trafficking systemCytoskeletal transport machineryVesicular transport machineryNucleocytoplasmic transport machineryMolecular motor system

Inhibition of microtubule polymerization or depolymerization (e.g., taxanes, vinca alkaloids); antagonism of nuclear export protein XPO1 (e.g., Selinexor); inhibition of kinesin motor proteins involved in mitotic spindle assembly (e.g., KSP inhibitors); disruption of dynein-mediated retrograde transport.