Overview: Cell messaging

CH 11: Cell Communication Cell-to-cell communication is essential for both multicellular and unicellular organisms Biologist have discovered some universal mechanism of cellular mechanism of cell regulation Cells most often communicate w/ each other via chem. signals For Ex, fight-or-flight response is triggered by a signal molecule called epinephrine

Key Concepts

C 11.1: external signals are converted to response within the cell 11.2: Reception: a signaling molecule binds to receptor protein, causing it to change in shape 11.3: Transduction: cascades of molecular interactions relay signals from receptors to target
molecule in the cell 11.4: Response: cell signaling leads to regulation of transcription of cytoplasmic activities 11.5: Apaptosis integrates multiple cell signaling pathways

C 11.1: External signals are converted to responses within the cell

evolution of cell signaling

- signal transduction pathway is a series of steps by which a signal on a cells surface is converted into a specific cellular response - signal transduction pathways convert signals on a cells surface into cellular responses - Pathway similarities suggest ancestral heritage from prokaryotes to euk. - concentration of signaling molecules allow bacteria to detect population density

Local and Long-distance signaling

cells in multicellular organism

communicate by chem. m messengers A&P cells have cell junctions that directly connect cytoplasm of adjacent cells In local signaling, A cells may communicate by direct contact , or cellcell recognition Many cases cells communicate using local regulators, messenger molecules travel short distances In long distance signaling, A&P use chem. called hormones Ability to respond to signal depends whether or not it has receptor specific to that signal Earl w. Sutherland discovered how hormone epinephrine acts on cells and suggested that cells receiving signals through three processes - Reception - Transduction - Response \

C 11.2: Receotion: a signal molecule binds to a receptor protein causing it to change shape Receptors in Plasma membrane

Binding between signal molecule (ligand) and receptor is specific and shape changing in a
receptor is of the initial transduction on of the signal Most signal receptors are plasma membrane proteins, but there are intracellular receptors as well

Most water-soluable signal molecules bind to specific sitens on receptor proteins in plasma mem. 3 types of membrane proteins
- G protein- coupled receptors - Receptor tyrosine kinesis - ion channel receptors

G protein-coupled receptors the receptor

A G protein-coupled receptor is a plasma membrane recpror that works with the help of a G
protein G protein acts as on/off/switch: if GDP is bound, the G proteins is inactive receptor tyrosine kinases are membrane receptors hat attach to phosphates and can trigger multiple signal transductions A ligand-gated ion channesl receptor acts as a gate when receptor change shape When ligand attaches, it opens gate to let in specific ions like Na+ and Ca2+

Intracellular Receptors

Some receptors are intracellular, found

in cytosol or nucleus of taraget cell Small of hydrophobic chem. messengers (steroids and thyroid hormone of animals) can readily cross membrane & activate receptor

C 11.3: Transduction: Cascades of molecular interaction relay signals from receptors to target molecules in the cell Signal transduction pathways

Signal transduction pathways

- molecules that relay singnal from receptor to respose are mostly proteins - like falling dominoes, receptor activate proteins, then activate another receptor, until response At each step, signal transduced into different form, usually a shape change in a protein Multistep pathways can 1) amplify signal 2) provide for coordination and regulation 1) proteins can be phosphorylated / dephoshorylated 2) second messangers (small molecules and ions) a)Cydic AMP (and cGMP) b) Calcium ions

Protein phosporylation and dephosphorylation

in many pathways signal is transmitted by cascade of protein phosphorylations

- proteins kinases attach phosphates from ATP to protein, process called phosphrylation - protein phosphates removes phosphates from proteins, process called dephosphorylation phosphorylation and dephosphorylation system acts as molecular switch, turn on&off as required

Cyclic AMP (and cGMP)

cyclic AMP (cAMP) and cyclic GMP (cGMP) are some of

most widely used second messengers Adenylyl cyclase (or guanylyl cyclase e), enzyme in plasma membrane, converts atop to cAMP I response to extracelluar signal signals trigger cAMP formation camp pathway include G proteins G pro.-coupled receptors Pro. In kinases cAMP usually activates proteins kinase A, that phosphorylates other proteins. Further regulation is provided by G- pro. that inhibit adenylyl cyclase

Calcium Ions and Inositol Triphosphate

Calciumions (Ca2+) act as second messenger in many pathways Calcium is an important second messenger bcc its concentration is regulated Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol
(DAG) as additional second messengers

Nuclear and Cytoplasmic Responses

Change in cell activity in response

to a signal may occur in cytoplasm or may involve the nucleus Many signal pathways regulate sunthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus Final activated molecule may function as a transcription factor Other pathways regulate enzyme activity Signaling pathways can also affect the overall behavior of a cell, for Ex: changes in cell shape Cell shape during directional growth in yeast

Fine tuning of the response

Multistep pathways have 2 important benefits:

-amplification of signal (and thus the response) -contributing to the specificity of the response Four aspects of fine-tuning to consider - Amplification of signal via enzyme cascades that magnify the response - Specificity of the response - overall efficiency of response, enhanced by scaffolding proteins - Termination of signal

The specificity of cell signaling and coordination of the response

diff kinds of cells have diff collection of proteins; help cells to detect and respond to diff ones Even same signal can have diff effects in cells with diff proteins and pathways Pathway branching and cross-talk further help the cell coordinate incoming signals Scaffolding proteins are large relay proteins to which other relay proteins are attached that group
different kinasses involved in the same pathway

Signaling efficiency: scaffolding proteins and signaling complex Termination of the signal

Inactivation mechanisms are essential aspect of cell signaling If concentration falls, fewer receptors will be bound Unbound receptors revert to an inactive state Apoptosis programmed or controlled cell self-destruction (suicide-?) where a cell is chopped and
packaged into vesicles that are digested by scavenger cells

C 11.5: apoptosis (programmed cell death) integrates multiple cellsignaling pathways Apoptosis in the soil worm Caenorhabditis elegans

Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells Apoptosis is important in shaping
an organisms during embryonic development In C. elegans, apoptosis results when proteins that accelerate apoptosis override those that put the brakes on apoptosis

Apoptotic pathways and the signals that trigger them

Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis Apoptosis can be triggered by
- and extracellular death-signaling ligand - DNA damage in the nucleus - protein misfolding in the endoplasmic reticulum Apoptosis evolved early in animal evolution and is essential for the development and mainteneve of all animals Apoptosis may be involved in some diseases (for Ex: Parkinsonss and Alzheimers); interfere with apoptosis may contribute to some cancers

You should now be able to:

1.Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system 2.Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels 3.List two advantages of a multistep pathway in the transduction stage of cell signaling 4.Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell 5.Define the term second messenger; briefly describe the role of these molecules in signaling pathways 6.Explain why different types of cells may respond differently to the same signal molecule 7.Describe the role of apoptosis in normal development and degenerative disease in vertebrates