Cytoskeleton.pdf

Cytoskeleton Microfilaments, composed of actin, assemble as actin monomers (G-actin) add to the growing end of a filament (F-actin). This polymerization is regulated by actin-binding proteins (ABPs) like profilin and cofilin. Proteins such as tropomyosin and troponin control actin's interaction with...

Cytoskeleton Microfilaments, composed of actin, assemble as actin monomers (G-actin) add to the growing end of a filament (F-actin). This polymerization is regulated by actin-binding proteins (ABPs) like profilin and cofilin. Proteins such as tropomyosin and troponin control actin's interaction with myosin, and small GTPases like Rho regulate actin organization. Microtubules, formed by tubulin heterodimers, undergo dynamic assembly with protofilaments forming a hollow tube. Assembly occurs at the microtubules plus end. Regulation involves microtubule-associated proteins (MAPs) stabilizing microtubules, GTP hydrolysis for stability, and motor proteins like dynein and kinesin facilitating intracellular transport. Intermediate filaments, including keratins and vimentin, assemble as coiled-coil dimers to form stable filaments. Unlike microfilaments and microtubules, their assembly is less dynamic. Phosphorylation and dephosphorylation of specific sites on intermediate filament proteins regulate their assembly and disassembly. Differences: Microfilaments are composed of actin proteins, microtubules are made up of tubulin proteins, and intermediate filaments consist of various proteins depending on the type. Additionally, microtubules play a pivotal role in cell division, forming the mitotic spindle, while microfilaments contribute to cytokinesis. In contrast, intermediate filaments provide structural support during cell division but are not directly involved in the process. Despite their differences All three components contribute to the cell's structural support, helping maintain cell shape and integrity. Their dynamic nature allows for rapid reorganization, facilitating cellular processes such as cell motility, division, and intracellular transport. Microfilaments, primarily composed of actin, play roles in individual cells by contributing to cell shape, motility, and the dynamic process of cytokinesis during cell division. In tissues, microfilaments, especially actin, are essential for the structural integrity of epithelial cells, influencing resilience. Microtubules, formed by tubulin proteins, serve crucial functions at the cellular level by organizing the mitotic spindle during cell division and facilitating intracellular transport. In tissues, microtubules contribute to the structural support of cells, helping determine cell shape, and play essential roles in specialized tissues like muscle, where they are integral to sarcomere organization. Intermediate filaments, with various proteins such as keratins and vimentin, provide structural stability to individual cells and contribute to the integrity of tissues subjected to mechanical stress. In tissues, intermediate filaments are abundant in epithelial tissues, adding resilience, and are essential in neuronal tissues, supporting the structural integrity of neurons. The extracellular matrix (ECM) is a complex network of molecules surrounding cells, comprised of fibrous proteins like collagen and elastin, as well as proteoglycans and glycoproteins. It serves as a scaffold, providing structural support to cells while influencing their behavior through signaling pathways. Cell-ECM interactions, facilitated by molecules like integrins, allow cells to adhere to and interact with the ECM, triggering intracellular signaling that regulates various cellular activities. Tissue formation involves coordinated cellular behaviours, including proliferation, migration, and differentiation, with cells actively secreting ECM components. Tissues undergo continuous remodelling and repair processes, where cell-ECM interactions play a pivotal role in maintaining tissue homeostasis. integrins and Cell Adhesion: Integrins, cell surface receptors, play a crucial role in cell-ECM interactions by recognizing specific ECM molecules like fibronectin and collagen. Activation of integrins results in the formation of focal adhesions, adhesive complexes that physically connect the cell to the ECM, allowing for dynamic interactions. Focal Adhesions and Signaling: Focal adhesions, multi-protein complexes formed at sites of integrin-ECM attachment, serve as signaling hubs. They initiate intracellular signaling cascades, activating pathways like the Rho GTPase pathway, which influences cytoskeletal dynamics and cell motility. Focal adhesions also play a key role in coordinating cellular responses to the ECM. ECM-Mediated Signaling Pathways: Integrin engagement activates kinases such as focal adhesion kinase (FAK) and integrin-linked kinase (ILK), leading to phosphorylation of downstream targets. This activation influences various cellular processes, and ECM signaling can regulate gene expression through the activation of transcription factors like nuclear factor kappa B (NF-κB), impacting inflammatory responses and cell survival. Cell Migration and ECM Interactions: Integrin-mediated interactions with the ECM dynamically regulate cell migration. These interactions influence the organization of the cytoskeleton, resulting in changes in cell shape and the ability to navigate through the ECM. Integrins play a pivotal role in the dynamic regulation of cell adhesion and detachment during processes like cell migration. Stem Cell Fate and ECM: The ECM provides a microenvironment or niche for stem cells, influencing their fate decisions. The composition of the ECM affects whether stem cells differentiate into specific cell types or remain undifferentiated. Integrin-mediated signaling in the stem cell niche guides differentiation, with ECM molecules acting as signals that direct stem cells toward specific lineages.