CH 11: Cell Communication Overview: Cell messaging Key Concepts C 11.1: External signals are converted to responses within the cell Local and Long-distance signaling C 11.2: Receotion: a signal molecule binds to a receptor protein causing it to change shape Receptors in Plasma membrane

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 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 evolution of cell signaling

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

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 cell-cell 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

\ 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

Intracellular Receptors C 11.3: Transduction: Cascades of molecular interaction relay signals from receptors to target molecules in the cell Signal transduction pathways Protein phosporylation and dephosphorylation Cyclic AMP (and cGMP)

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+

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

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 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 (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 Nuclear and Cytoplasmic Responses

Fine tuning of the response The specificity of cell signaling and coordination of the response Signaling efficiency: scaffolding proteins and signaling complex Termination of the signal C 11.5: apoptosis (programmed cell death) integrates multiple cell-signaling pathways Apoptosis in the soil worm Caenorhabditis elegans

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 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 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

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 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 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 You should now be able to:

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: Parkinsons’s and Alzheimer’s); interfere with apoptosis may contribute to some cancers

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