Cytoskeletal Signaling

Cytoskeleton refers to the structure of protein fiber networks in eukaryotic cells. It was found to be late, mainly because the general electron microscope preparation was fixed at a low temperature (0-4 ° C), and the cytoskeleton was depolymerized at a low temperature. It was not until the 1960s that glutaraldehyde was fixed at room temperature until the objective existence of the cytoskeleton was gradually recognized. The cytoskeleton plays an important role not only in maintaining cell morphology, bearing external forces, but also maintaining the order of the internal structure of the cell, and is also involved in many important life activities (Fig. 1), such as: cytoskeletal traction chromosome separation in cell division, In the transport of cellular material, various vesicles and organelles can be transported along the cytoskeleton; in muscle cells, the cytoskeleton and its binding proteins form a dynamic system; in leukocyte migration, sperm swimming, nerve cell axons and The extension of dendrites is related to the cytoskeleton. In addition, the cytoskeleton directs the synthesis of cell walls in plant cells. The cytoskeleton is composed of microfilaments, microtubules, and intemediate filaments. Microfilaments define cell surface characteristics that allow cells to move and contract. The microtubules determine the location of the membrane-enclosed organelle and serve as a guide for the transport of the bubble. The intermediate fibers give the cells tension and shear resistance. Microfilaments, microtubules, and intermediate fibers are located in the cytoplasm, also known as the cytoplasmic skeleton, which are bound together by weaker non-covalent bonds of monomeric proteins to form fiber-type polymers, which are easy to assemble and disassemble. This is what is necessary to achieve its function. The broad-based cytoskeleton also includes a nucleoskeleton, a nuclear lamina, and an extracellular matrix, forming an integrated network structure that runs through the nucleus, cytoplasm, and extracellular. Figure 1 shows the main function of the cytoskeleton. The cytoskeleton is the structural basis of cell function. In the process of external stimulation or cell division and differentiation, the morphological changes of cells are correspondingly changed. This is inseparable from the dynamic changes of the cytoskeleton of signaling regulation. of. The cytoskeleton acts as a dynamic protein fiber network structure in eukaryotic cells, consisting of microfilaments (MF), microtubules (MT) and intermediate filaments (IF). MF is a polymer composed of actin polymerization, which is widely found in eukaryotic stress fibers, focal adhesions, pseudopods and contractile rings. Its structural component is globular actin (G-actin). Under the action of ATP and a variety of microfilament-related proteins, through the continuous assembly and depolymerization of filamentous actin (F-actin), it is involved in the regulation of cell morphology, adhesion, migration and cytokinesis. MT is composed of α-tubulin and β-tubulin, which assembles into a hollow tubular structure under the action of microtubule-associated proteins, and plays an important role in intracellular material transport and cytokinesis. The MF and MT cytoskeleton are interrelated and interdependent and participate in the regulation of cellular behavior (Bailly M, 2002; Miranti CK, 2002). Cell migration is a key step in the invasion and metastasis of malignant tumors. The cytoskeleton and its binding proteins are the material basis of the cell migration process. The directional movement of cells requires the participation of the cytoskeleton, especially the microfilament skeleton composed of actin. MF and MT not only play an important role in stabilizing cell morphology, stimulating external force stimulation, maintaining the order of internal cell structure, but also participating in regulating cell migration, adhesion, division and intracellular signal transmission. Among them, the interaction between cAMP-mediated signaling pathway and cytoskeleton is closely related to cell proliferation, apoptosis, adhesion, migration and other cellular behaviors. cAMP-dependent protein kinase A (PKA) acts as a cAMP-dependent major target protein. , participated in these processes. PKA activates RhoA by phosphorylation. In addition to further activation of the downstream pathway, RhoA enhances binding to RhoDDI diphosphate inhibitory factor (RhoGDI), thereby inhibiting RhoA activity in reverse (Mehlen, P, 2006). . Integrin is an important receptor on the cell surface that has both adhesion and signal transduction functions. It is a heterodimer composed of α and β subunits through non-covalent bonds. Extracellular matrix proteins such as fibronectin, laminin and collagen are the major ligands; secondly, some cell surface molecules, soluble proteins, etc., can also bind to integrins. By combining the extracellular and intracellular segments with the cytoskeleton, signal transduction molecules and other proteins, the integrin is a bridge that mediates bidirectional information transfer between the inside and outside of the cell. Integrins can be bidirectionally signal transduced with the cytoskeleton. (1) From the cytoskeleton to integrins, integrins are dispersed on the cell surface when not bound, and are not connected to the actin cytoskeleton. Ligand binding in ECM is linked to the cytoskeleton through its intracellular domain and clustering occurs. (B) From integrins to the cytoskeleton, integrin can feedback regulate the assembly of the cytoskeleton, and integrin-mediated adhesion itself can activate the Rho family of small G proteins (Mitra SK, 2005; Larsen M, 2003; Turner CE, 2000).