Overview: The Cellular Internet Cell-to-cell communication is essential for organisms Biologists have discovered some universal strategies and mechanisms of cellular regulation Response is determined by combined effects of multiple signals

Yeast Mating-a classic system Receptor  factor a factor a   a Exchange of mating factors Yeast cell, mating type a Yeast cell, mating type  Mating New a/  cell a/  An example of cell signalling

Yeast Mating System Exemplifies Cell Communication Aka Signal Transduction Simple but all the key features are present Reception, Transduction, Response

A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response

Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes The concentration of signaling molecules allows bacteria to detect population density Quorum-sensing in Vibrio fischerii

When cells are touching signalling is easy Plasma membranes Gap junctions between animal cells (a) Cell junctions Plasmodesmata between plant cells (b) Cell-cell recognition

In many other cases, cells must share information with cells they are not touching They use (1) local regulators, messenger molecules that travel only short distances And (2) chemicals called hormones for long- distance signaling

Local signaling in animals is either paracrine or synaptic Local signaling Target cell Secretory vesicle Secreting cell Local regulator diffuses through extracellular fluid (a) Paracrine signaling (b) Synaptic signaling Target cell is stimulated Neurotransmitter diffuses across synapse Electrical signal along nerve cell triggers release of neurotransmitter Both are short-range but synaptic signaling occurs only in the nervous system

Long-distance signaling usually involves different organs communicating Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (2) Hormonal signaling The messenger molecules are called hormones

EXTRACELLULAR FLUID Plasma membrane CYTOPLASM Receptor Signaling molecule Relay molecules in a signal transduction pathway Activation of cellular response TransductionResponse 2 3 Reception 1 There are three stages in cell signaling Reception Transduction Response

RECEPTION TRANSDUCTION RESPONSE

The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins 3 examples from many possible

A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive GTP/GDP are chemically very similar to ATP/ADP but contain Guanine not Adenine Reception- Example I

Mechanism of G protein coupled reception G protein-coupled receptor Plasma membrane Enzyme G protein (inactive) GDP CYTOPLASM Activated enzyme GTP Cellular response GDP P i Activated receptor GDP GTP Signaling molecule Inactive enzyme The relay protein is called a “G Protein”

Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines Has intra- and extracellular domains, also membrane domain A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Kinase is an enzyme that attaches a phosphate to a substrate Reception- Example II

Signaling molecule (ligand) Ligand-binding site  Helix Tyrosines Tyr Receptor tyrosine kinase proteins CYTOPLASM Signaling molecule Tyr Dimer Activated relay proteins Tyr P P P P P P Cellular response 1 Cellular response 2 Inactive relay proteins Activated tyrosine kinase regions Fully activated receptor tyrosine kinase 6 6 ADP ATP Tyr P P P P P P

A ligand-gated ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na + or Ca 2+, through a channel in the receptor Reception- Example III

Ligand- gated ion channel Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed 3 2 1

Signal Transduction: an example of a key type of transduction pathway and response An example of a response Reception Transduction Response Binding of epinephrine to G protein-coupled receptor (1 molecule) Inactive G protein Active G protein (10 2 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (10 2 ) ATP Cyclic AMP (10 4 ) Inactive protein kinase A Active protein kinase A (10 4 ) Inactive phosphorylase kinase Active phosphorylase kinase (10 5 ) Inactive glycogen phosphorylase Active glycogen phosphorylase (10 6 ) Glycogen Glucose-1-phosphate (10 8 molecules) This type of signal transduction pathway is called a cascade Cyclic AMP is the key inside the cell. (Do not memorize this cascade)

Adenylyl cyclase Pyrophosphate P P i ATP cAMP Phosphodiesterase AMP Cyclic AMP is the “second messenger”

Ethylene Response in plants Identify: Reception, Transduction, Response