Chemokines and Recirculation - Group 3 PDF

BIOLOGICAL ACTION OF CHEMOKINES 1. Inactive State (A): - The GPCR is embedded in the cell membrane, with its extracellular side facing the outside of the cell. - In this state, the G-protein is inactive and consists of three subunits: Gα, Gβ, and Gγ, which are bound together. - The Gα subunit...

BIOLOGICAL ACTION OF CHEMOKINES 1. Inactive State (A): - The GPCR is embedded in the cell membrane, with its extracellular side facing the outside of the cell. - In this state, the G-protein is inactive and consists of three subunits: Gα, Gβ, and Gγ, which are bound together. - The Gα subunit is bound to GDP, indicating the inactive form of the G-protein. 2. Chemokine Binding (B): - When a chemokine (a signaling molecule) binds to the GPCR, the receptor undergoes a conformational change. - This change causes the G-protein to exchange GDP for GTP, activating the Gα subunit. - The Gα subunit dissociates from the Gβγ dimer, and both can now activate downstream signaling pathways. 3. Active State (C): - The Gα subunit and the Gβγ dimer can independently trigger different signaling cascades. - The Gα subunit typically interacts with adenylyl cyclase (AC), decreasing the levels of cyclic AMP (cAMP). - The Gβγ subunit can also activate downstream signaling, such as kinases. - These signaling cascades lead to various physiological responses, including chemotaxis, cell survival, apoptosis, and transcription. THE TWO TERMINAL IN GPCR 1. NH₂ (Amino Terminus): - This is the N-terminal of the GPCR protein, which is located on the extracellular side (outside the cell membrane). - It interacts with signaling molecules such as chemokines or other ligands that bind to the receptor, initiating the activation process. 2. COOH (Carboxyl Terminus): - This is the C-terminal of the GPCR, located inside the cell (cytoplasmic side). - It plays a key role in interacting with intracellular proteins, including the G-protein complex (Gα, Gβ, Gγ), facilitating signal transduction inside the cell. IMPORTANCE OF LYMPHOCYTE RECIRCULATION  Lymphocyte recirculation is a vital process that plays a crucial role in maintaining immune homeostasis and ensuring the efficient functioning of the immune response. The continuous surveillance of the body for pathogens, activation and proliferation of immune cells, maintenance of immune memory, regulation of immune responses, and maintenance of immune tolerance are all critical functions that rely on the recirculation of lymphocytes. Any disruption to this process can lead to impaired immune function, increased susceptibility to infections, and the development of autoimmune diseases. Key Steps in Lymphocyte Recirculation:  Entry via HEVs: Lymphocytes move from blood into lymph nodes or Peyer's patches.  Lymphatic Drainage: After performing surveillance in the lymph nodes or other tissues, they enter the lymphatic system.  Return via Thoracic Duct: They are eventually returned to the blood through the thoracic duct, allowing them to continue patrolling the body. REFERENCES Lymphocyte recirculation. Lymphocyte Recirculation - an overview | ScienceDirect Topics. (n.d.-a). https://www.sciencedirect.com/topics/immunology-and- microbiology/lymphocyte-recirculation Tripathi, D. K., & Poluri, K. M. (2020, March 1). Molecular insights into kinase mediated signaling pathways of chemokines and their cognate G protein coupled receptors. IMR Press. https://www.imrpress.com/journal/FBL/25/7/10.2741/4860/htm https://youtu.be/AqyDzRvasNM?si=ZAuqqZPveqaDjtQR https://youtu.be/GKbJkFoO9BQ?si=IoKOyBPdbfbS9Zig