Cellular Messaging PDF

Cellular Messaging Cells can send signal to each other and interpret signals they receive from other cells and the environment. The sames mall set of cell-signaling processes occurin a variety of species. Neurotransmitters = language Local and Long Distance Signalling Local Signalling contact: Co...

Cellular Messaging Cells can send signal to each other and interpret signals they receive from other cells and the environment. The sames mall set of cell-signaling processes occurin a variety of species. Neurotransmitters = language Local and Long Distance Signalling Local Signalling contact: Communications between nearby cells can be done via direct contact Cell junctions Cell-cell recognition-between membrane- bound cell-surface molecules In many cases, animal cells communicate using secreted messenger molecules that only travel short distances: Paracrine signalling: a secreting cell acts on nearby target cells by producing molecules of a local regulator. E.g. growth factor Synaptic signalling: a nerve neurotransmitter cell releases molecules into a synapse , stimulating the target cell. E.g. neurotransmittersin nervous system Long-Distance Signalling In long-distance signalling, both animals and plants use hormones. Hormonal signalling in animals is called endocrine signalling- specialized cells release hormone molecules that travel to other parts of the body via the vascular system. The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal. Gap junctions = neurotransmitters and heart Reception The signaling molecule (ligand) is complementary in shape to a specific site on the receptor protein. 1. Ligand binds to the reception site. 2. Ligand binding causes the receptor to change in shape. 3. The change in shape activates the receptor,resulting in downstream effects. Most receptors are plasma membrane proteins (A), while others are located inside the cells(B). A. Plasma Membrane Receptors three major types of plasma membrane receptors: G-protein-coupled receptors(GPCR) Receptor tyrosine kinase (RTK) Ion channel receptors The largest family of human cell surface receptors are GPCR. Extracellular receptor (hydrophilic bisa nya lewat ini) GProtein-CoupledReceptors (GPCR) GPCR is a cell-surface transmembrane receptor that works with the help of a G protein- protein that binds GTP molecules GTP is Guanosine triphosphate-rich in energy GPCRs vary in the binding sites for their ligands and for the different types of G protein inside the cell-> diverse function Secondary protein structure of GPCR consists of 7 transmembrane 𝛂-helices- hydrophobic regions Processes that depend on GPCR: vision,smell, taste. E.g. rhodopsin (GPCR) that responds to light signal received by rod cells. Ligan bind with G protein -> G protein buang GDP trus bind he G protein trus dapet GTP -> GTP then move to the enzyme (cellular response) -> inactivatte when bind with GDP https://youtu.be/xT0mAQ4726s?si=QesNmmzFe0HQAbph Receptor Tyrosine Kinase RTKs are characterized by having an enzymatic activity-> (kinase) catalyzes the transfer of phosphate group. Active RTK receptors always act as a dimer. The part of an RTK that is extending into the cytoplasmacts as a tyrosine kinase-> catalyzes the transfer of phosphate group from ATP to the tyrosine on the other subunit. One RTK complex may activate 10 or more different transduction pathways and cellular responses. E.g. growth factor receptor-> cell growth, cell division, differentiation 2 Ligand site if it is bind it will make a dimer (dimerization) -> will add phosphate -> it will be reconized with the relay proteins -> cellular response https://youtu.be/0mKZRAt0GZg?si=xztsCuCOMl_AEtYO Ion Channel Receptor Ion channel receptor has a “gate” that opens orcloses when a ligand binds to the binding site and the receptor changes its shape → allowing or blocking the flow of specific ions. Ion channel receptors have important roles in the nervous system. Some gated ion channels are controlled by electrical and mechanical signals instead of ligands. Gate is closed -> ligand binds with the receptor -> gate will open -> ions will come in (cellular response) For example gatenya itu negative datanglah Na yang + dia bakal nempel ke gate trus ++++ ke gatenya. Alias itu stimulus buat gatenya buka Intracellular receptor Locations: cytoplasm or nucleus. 1. A signalling molecule (usually hydrophobic small and ) passes through the plasma membrane into the nucleus or cytoplasm. 2. Binds to an intracellular receptor, forming signal-receptor complex. 3. Cellular responses begin. E.g., signalling molecule: steroid hormones Steroid bakal masuk ke plasma membrane -> ikat dengan receptor -> masuk ke nucleus -> transkrip ke mrna -> mrna ke protein https://youtu.be/wJk7nRccLbc?si=tR0RAi_qwJNlrI8W Transduction Transduction stage is usually a multistep pathway involving many molecules. These steps include: A. Protein activation by the addition or removal of phosphate groups (phosphorylation/dephosphorylation). B. Release of other small molecules that act as messengers. Multistep pathways provide more opportunities for coordination and regulation of the cellular responses A. Protein Phosphorylation and Dephosphorylation Phosphorylation and dephosphorylation are used to regulate protein activity (on/off, up/down). Phosphorylation An enzyme that transfers phosphate groups from ATP to a protein is called protein kinase. Many of the relay molecules in signal transduction pathways are protein kinases → often act on other protein kinases in the pathway. Dephosphorylation An enzyme that removes phosphate groups from a protein is called protein phosphatase. Protein phosphatase functions: Provide the mechanism for turning off the pathway when the initial signal is no longer present. Make protein kinases available for reuse, enabling cell to respond again to an extracellular signal Phosphorylation cascade Control exprerssion Intinya speperti estafet energi https://youtu.be/D4QXR8Exzjo?si=JUlrmzt7G8kZVXZR https://youtu.be/9s9GJx6XJZM?si=Zfy2lGn5vjaRLH1t B. Small Molecules and Ions as Second Messengers First messengers are extracellular molecules, often hormones or neurotransmitters. In contrast, second messengers are intracellular molecules that transmit signals from cell membrane receptors to targets within the cell (amplification, first messenger big second messenger) Many signaling pathways initiated by GPCR and RTK involve small, non-protein, water-soluble molecules or ions → second messengers These second messengers can rapidly spread throughout the cell by diffusion. The most widely used second messengers are: Cyclic AMP. Calcium ions. Cyclic AMP (cAMP) Pathway 1. An extracellular signal binds to a specific receptor protein (GPCR). 2. The GPCR activates G protein (GTP replaces GDP). 3. G protein activates adenylyl cyclase. 4. Adenylyl cyclase converts ATP to cAMP (cyclic AMP). 5. cAMP broadcasts the signal to cytoplasm. 6. Immediate effect: the activation of protein kinase A. 7. Cellular responses begin First messenger (ligand) bind to a Gprotein -> G protein GTP -> enzyme nya ubah ATP ke cAMP -> activate protein kinase A -> cellular response https://youtu.be/Nt2r5R0ZO5U?si=PqIv_kkMdsdq84cS IP3 and Calcium Ions Phosphatidylinositol 4,5-bisphosphate (PIP2). Diacylglycerol (DAG). Inositol 1,4,5-triphosphate (IP3) IP3 an Calcium ions Cellular responses to Ca2+ release into the cytoplasm: Muscle contraction. Fusion and exocytosis of enzyme carrying vesicles. Glycogen metabolism. https://youtu.be/p8JGpbxyxHE?feature=shared Responses Nuclear and Cytoplasmic Responses A signal transduction pathway leads to the regulation of one or more cellular activities. The responses may occur in the nucleus or in the cytoplasm. In the nucleus: The final activated molecule may function as a transcription factor (TF), which results in gene transcription (synthesis of one or more specific mRNA → protein production) or inactivation In the cytoplasm: Other signaling pathways regulate the activity of proteins. These directly affect proteins that function outside of the nucleus. E.g., A signal may cause the opening or closing of an ion channel in intracellular membrane or a change in cell metabolism-increased level of glucose in the blood due to glycogen breakdown by epinephrine/adrenaline (hormone). Regulation The response of signaling pathway is not simply turning on or off. There are four aspects of signal regulation: 1. Signal amplification. 2. Signaling specificity. 3. Signaling efficiency. 4. Signal termination Signal Amplification Elaborate enzyme cascade amplify a cell’s response to a signal. At each catalytic step in the cascade, the number of activated products can be much greater than in the preceding step. This effect is caused by the protein that persists in the active form for long enough before they become inactive again. A small number of signaling molecules can lead to release of many molecules https://youtu.be/PT5ptJZJ-58?si=zyl_lIEviKGjBwZd Signaling Specificity Different kinds of cells turn on different sets of genes. The response of a particular cell to a signal depends on its particular collection of signal receptor proteins, relay proteins, and response protein. Two cells that respond differently to the same signal differ in one or more of the proteins that handle and respond to the signal. Signaling Efficiency Efficiency of signal transduction is increased by the presence of scaffolding proteins. Scaffolding proteins are large relay proteins to which several other relay proteins are simultaneously attached. Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway. This protein acts as a branch point and an important intersection point in a complex signal transduction network. Signal Termination In multicellular organisms, for a cell to remain capable of responding to incoming signals, each molecular change in its signaling pathways must last only for a short time. The ability of a cell to receive new signals depends on the reversibility of the changes produced by prior signals. Binding of signaling molecules to receptors is reversible So intinya biar bisa resey and capture signal lagi Apoptis Cells that are infected, damaged, or have reached the end of their functional lifespan often undergo “programmed cell death”. During apoptosis, cellular agents chop up the DNA and fragment of the organelles and other cytoplasmic components. Cell shrinks; the cell parts are packaged in vesicles that are engulfed and digested by a specialized scavenger cells. Apoptosis protects neighboring cells from damage that they would otherwise suffer if a dying cell leaked out its contents Apoptotic Pathways and the Triggering Signals The signal that triggers apoptosis can come from either outside or inside the cell. Outside: Outside the cell, signaling molecules released from other cells can initiate a signal transduction pathway. This pathway activates genes and proteins responsible for carrying out cell death. E.g., Tumor necrosis factor (TNF) - secreted by immune cells - signals tumor cells to start apoptosis. Inside: Inside the cell, a series of protein-protein interactions can pass along signals that trigger cell death. The first signal comes from the nucleus, which is generated when DNA has suffered irreparable damage. The second signal comes from the ER when excessive protein misfolding occurs.