Cell Communication -017

Overview

Cell communication requires a signal(ligand) and a receptor that binds to that signal

  • Change in behavior means:

    • Expressing certain genes

    • Carrying out certain reactions

  • Cell communication is especially critical for multicellular organisms

Neutrophil Chase

  • Neutrophil is a white blood cell(Immune cell)

  • It consists of red blood cells and bacteria

  • The bacteria bounces around in the liquid they are secreting chemicals; meaning they are signaling to the Neutrophil

    • Then the bacteria gets sent to the lysosome of the Neutrophil to get broken down and recycled 

Fight-or-Flight signaling

  • One signal, different responses in different cells

  • Coordinated action among many different organs

  • Adrenaline is produced in the adrenal gland and that gets released into the bloodstream to reach other organs(all have adrenaline receptors)

    • This signaling allows for the appropriate coordinated action

Unit 3 Model to focus on mutations associated with cancer

  • Eukaryotic cells typically only divide in response to a growth signal

  • Mutations in receptor kinase pathways associated with cancer(abnormal, unregulated cell division)

  • Cellular response: Cell division

Key stages in cell signaling

  • Physical interactions and changes in protein shape are key elements of cell communication

  • Different signals in the signal transduction can lead to different responses in the termination

  • Arrows can mean different things in these models

  • Use context and knowledge of how pathways work to infer the meaning 

  • Possible meanings

    • Chemical reactions occuring

    • Molecule movements

    • Steps occurring in a specific sequence

    • One molecule interacting with activating with another molecule

Receptors come in many shapes and sizes

  • What do they have in common

    • Receptors all bind to specific ligands

    • Ligand binding mediated manily using intermolecular forces

  • Receptors all change shape after binding  the ligand

    • Receptor activation 

    • Change in shape is a part of relaying the signal

Summary

  • Cells change their behavior based on signals(ligand) in the environment

  • Cell communication requires a ligand and a receptor

    • Receptors bind to specific ligands using primarily weak intermolecular forces

  • Common element in signaling pathways: receptors and signal transduction proteins change shape in response to a signal

    • Different structure results in a different function

Mechanisms of signal transduction and termination

Receptor activation is a molecule switch:

  • Ligand binding leads to a change in receptor shape

G proteins are regulated by binding to GDP or GTP

  • GDP or GTP binds using weak intermolecular foreces to G proteins

  • Change in protein structure that changes protein function

Some receptors use G proteins to pass along the message

  • Activation of G protein: Exchange of GDP for GTP

  • Termination of G proteins: GTP hydrolyzed to DGP + Pi

Some G proteins activate the enzyme adenylyl cyclase(AC)

Adding or removing phosphates

  • Charged phosphates affect interactions among amino acids within the protein and with other molecules

  • Depending on the change in shape, phosphorylation can activate or inactivate

    • Change protein structure

    • Change protein function

  • Termination: reversal of activating reaction

Activating kinases phosphorylate other molecules

  • ATP is always the source of phosphates for kinase reactions

  • Termination: cAMP floats away from Phosphatase removes phosphates

Summary

  • Several common mechanisms of cell signaling(‘molecular switches’ that can be quickly activated or deactivated)

  • All signal transduction involves change in shape that result in changes in function to pass on the signal and generate a cellular response

    • Look for the physical change(change in shape) associated with each step

Key signaling features of intercellular and cell surface receptors

Receptors can be found on the cell surface or inside the cells

What types of ligands likely bind to receptors inside the cell

  • Nonpolar cells are able to move through the cell very easily

The cellular response for a steroid horomone is a change in gene expression(transcription and translation)

  • Ligand binding using primarily non-covalent interaction

  • Receptor activation(change in shape) after ligand binding

Cell-surface receptors must relay the signal through protein intermediates

  • Ligand binding using primarly non-covalent interactions

  • Receptor activation(change in shape) after ligand binding

  • Cellular response could be a change in the cytoplasm or a change in the nucleus

Ligand-gated ions channels allow specific ions to cross membranes when ligands are present

  • Example: ions channels that initiate muscle contractions

G protein coupled receptor signal transduction

  • G proteins, protein:protein interactions, second messengers, phosphorylation are all part of the signal transduction of GPCRs

    • Example: adrelanine signaling in flight or fight

Receptor kinase activation and intitail signal transduction

  1. Ligand brings together two monomers to form a dimer

  2. Each receptor acts as a kinase to phosphorylate the other receptor

Signal transduction

  1. The phosphorylated receptor dimer binds to signal transduction proteins in the cytoplasm

  2. Ras activated by GDP-GTP exchange

  3. Active Ras activates Map K3

  4. Map Kinase phosphorylation cascade

  5. MapK moves into the nucleus to phosphorylate transcription factors

Cellular Response

  1. Change in gene expression through altered transcription factor function

Simplified Receptor kinase pathway 

Example of receptor kinase signaling: cell division in wound healing 

  • Cells near the injury release PDGF, a growth factor protein

    • PDGF binds to receptors on skin stem cells 

Summary

  • Receptors are classified as cell-surfaced or intercellular

    • Cell surfavve receptors typically bind polar ligands, intracellular receptors typically bind nonpolar ligands

  • Steroid hormone receptors are a type of intracellular receptor

    • The cellular response to a steroid hormone is a change in gene expression

    • No signal transduction proteins required

  • Cell-surface receptors often require many proteins for signal transduction

    • Ligand-gated ion channels allow ions to cross membranes

    • G protein-coupled receptors activiate G protein and cause 2nd messengers to be produced as part of their signal transduction

    • Receptor kinase pathways use G proteins and phosphorylation in signal transduction

Signal amplification and termination

Complex signal transduction cascades are more common than intercellular signaling paths

Signal cascades allow for amplification and modulation of signals

  • Amplification: allows for a single intial signal to generate a large cellular response

  • Multi-step pathways: each step of the pathway is an opportunity for fine-tuning of signals

Termination of a GPCR pathway: every activating step must be inactivated

Signal termination is necessary to;

  • Stop the response to the initial signal

  • Allow the cell to respond to a new signal

Signal amplification occurs in the Receptor Kinase pathway

Termination: Every activated step must be inactived

Summary

  • Amplification and modulation of signal transduction are key advantages of multi-step signaling pathways

    • GCPR pathway amplification steps: G protein activation, production of cAMP, & phosphorylation of target proteins by active kinase

    • Receptor kinase pathway amplification: Map Kinase cascade

  • Signal termination is the effective reversal of the activation step

    • Required to end events in response to the signal and to allow new signals to be received

    • Failure to end the response to a cell division signal could be associated with cancer