Manipulating the Intracellular Trafficking of Nucleic Acids
Kenneth L. Brigham in Gene Therapy for Diseases of the Lung, 2020
Microtubules and actin filaments are believed to maintain intracellular distribution of organelles and to facilitate trafficking between organelles (for review see Ref. 62). Microtubules can be viewed as tracks for the movement of organelles and their cargo, where movement is driven by protein motors fueled by ATP (63,64). Microtubules radiate out from the microtubule organizing center (MTOC) into the peripheral regions of the cytoplasm, thus forming an extensive network of fibers throughout the cell (Fig. 2). The fast-growing ends (plus ends) of the microtubule are located at the cell periphery while the slow-growing ends (minus ends) are found at the MTOC. Differential distribution of organelles and transport vesicles are observed in the microtubule network with endosomes found near the plus ends at the cell periphery, whereas Golgi, late endosomes, and lysosomes are clustered near the minus ends near the nucleus.
Cell Structure and Functions
Malgorzata Lekka in Cellular Analysis by Atomic Force Microscopy, 2017
Microtubules are found in the cytoplasm of all eukaryotic cells where they are often observed to spread out radially from a microtubule-organizing center (MTOC) located near the nucleus (Fig. 2.17). The microtubules provide a strong scaffold that supports the cell and determines its shape. Most studies have concluded that microtubules play a positive role by regulating actin polymerization, transporting membrane vesicles or other organelles inside the cell, and/or facilitating the turnover of adhesion plaques. They can also form specialized structures such as centrioles, cilia, and flagella. Both cilia and flagella are cellular appendages, consisting of a core of microtubules enclosed in an extension of the plasma membrane, playing an important role in cellular locomotion.
The Aging of the Neuronal Cytoskeleton
Alvaro Macieira-Coelho in Molecular Basis of Aging, 2017
Microtubules, the third cytoskeletal component, are hollow tubes of 25 nm diameter formed by protofilaments composed of alpha and beta tubulin heterodimers. Like actin, the tubulins are highly conserved proteins and microtubule functionality is thus modulated by a family of associated proteins to adapt the microtubule cytoskeleton to the needs of different cell types. These proteins are called MAPs, for microtubule-associated proteins.9–11 The diversity of both tubulin isoforms and MAPs is highest in the brain, illustrating the importance of microtubules in neurons. Three main functions are executed by MAPs: microtubule stabilization, microtubule cross-linking, and organelle transport along microtubules. Like actin filaments, microtubules are mostly unstable filaments whose polymerization is often characterized as a dynamic equilibrium controlled by the concentration of tubulin monomers, GTP and calcium, as well as MAPs like the tau protein. The recently discovered gamma-tubulin acts as microtubule nucleating protein.12,13 This protein, whose concentration in individual cells is extremely low, is located in the microtubule organizing center (MTOC). The MTOC is an area normally located close to the nucleus from which microtubules irradiate throughout the cytoplasm. It is noteworthy that intermediate filaments also seem to irradiate from this area. However, the interaction of intermediate filaments with the MTOC has not been studied so far.
SPI2 T3SS effectors facilitate enterocyte apical to basolateral transmigration of Salmonella-containing vacuoles in vivo
Published in Gut Microbes, 2021
Marcus Fulde, Kira van Vorst, Kaiyi Zhang, Alexander J. Westermann, Tobias Busche, Yong Chiun Huei, Katharina Welitschanski, Isabell Froh, Dennis Pägelow, Johanna Plendl, Christiane Pfarrer, Jörn Kalinowski, Jörg Vogel, Peter Valentin-Weigand, Michael Hensel, Karsten Tedin, Urska Repnik, Mathias W. Hornef
Also, the role of the SPI2 T3SS for the positioning of intracellular S. Typhimurium seems to differ between non-polarized cells and polarized enterocytes. In non-polarized cells, SPI2 T3SS effectors were reported to mediate paranuclear localization.6,24,30 In contrast, our findings in highly polarized intestinal epithelial cells in vivo suggest that the interaction of SPI2 T3SS effector molecules with the microtubule network and trafficking machinery facilitates apical to basolateral transmigration. Importantly, this is fully consistent with the different organization of the microtubule network in polarized and non-polarized cells. In non-polarized cells, microtubules extend radially from the microtubule organizing center (MTOC) localized close to the paranuclear Golgi apparatus, whereas in polarized enterocytes they extend from the apical membrane to the basolateral side to facilitate vectoral vesicle transport.32 The continued presence of SPI2 T3SS mutant microcolonies mainly at the apical pole is also reminiscent of the appearance of subapical vesicles in genetic disorders of the intracellular trafficking machinery.33 Thus, the enhanced size and block in apical to basolateral transmigration of SPI2 T3SS mutant and somewhat less pronounced also for SifA mutant SCVs as well as the enhanced size of SseFG and PipB2 deficient S. Typhimurium SCVs suggest a critical role of the SPI2 T3SS and a contribution of the translocated effector molecules SifA, SseFG and PipB2 in the microtubule-mediated transport of the SCV through the epithelial cell in vivo.
Targeting Autophagy In Disease: Recent Advances In Drug Discovery
Published in Expert Opinion on Drug Discovery, 2020
Dasol Kim, Hui-Yun Hwang, Ho Jeong Kwon
In the final maturation/degradation step, autophagosomes traffic toward the microtubule-organizing center (MTOC) to fuse with lysosomes and degrade cargo through lysosomal hydrolases. Two essential processes are pivotal for proper autophagy turnover: (1) autophagosome-lysosome fusion, and (2) lysosomal hydrolase activation. Although the mechanism underlying autophagosome-lysosome fusion is currently unclear, it is under intense investigation. Factors involved in fusion include the endosomal sorting complexes required for transport (ESCRTs), soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE), ultraviolent radiation resistance-associated gene (UVRAG), Rubicon (RUBCN), small GTPase of the Ras-related protein 7 (RAB7), lysosomal associated membrane protein 2 (LAMP2), ion channels, and other tethering factors [13–17]. Because lysosomal enzymes are acid hydrolases (including proteases, glycosidases, nucleases, phosphatases, and lipases) that are active at acidic pH (~5) but not neutral pH, maintaining low pH is essential for ‘active lysosomes’ to induce sequential autophagic turnover. Accordingly, lysosomal ion channel proteins such as vacuolar-type H+-ATPase (V-ATPase) and transient receptor potential mucolipin 1 (TRPML1) play essential roles to maintain lysosomal ionic homeostasis and membrane potential, resulting in lysosome activation by hydrogen cation influx [18].
Microtubule affinity regulating kinase 4 promoted activation of the NLRP3 inflammasome-mediated pyroptosis in periodontitis
Published in Journal of Oral Microbiology, 2022
Lulu Wang, Wenchen Pu, Chun Wang, Lang Lei, Houxuan Li
Microtubules, which are components of the cytoskeleton system, are crucial in the activation of the NLRP3 inflammasome by providing the platform for the assembly of the NLRP3-ASC-caspase 1 complex [15,16]. Such an assembly process requires the accumulation of acetylated α-tubulin on the microtubules to create optimal sites near the endoplasmic reticulum [17,18]. Microtubule affinity regulating kinases (MARKs), which have four family members and share a similar structure, can phosphorylate microtubule-associated proteins (MAPs) such as MAP2, MAP4 as well as tau, thereby promoting microtubule dynamics [15,19,20]. MARK4 participates in the activation of the NLRP3 inflammasome by driving it to the microtubule-organizing center, leading to the formation of one large inflammasome speck complex [21]. MARK4 has been identified as a potential drug target for several diseases such as obesity [22,23], cancer [24–26], and metabolic disorders [16].
Related Knowledge Centers
- Cell Division
- Eukaryote
- Flagellum
- Microtubule
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- Cilium
- Meiosis
- Mitosis
- Chromosome
- Microtubule Nucleation