Cell Communication

Cell Signaling Cell-to-cell communication is essential for multicellular organisms Communicate by chemical messengers Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells In local signaling, animal cells may communicate by direct contact

Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells Cell junctions Cell-cell recognition

Signaling Local- paracrine, synaptic signaling Long-distance- hormonal signaling (endocrine) Local signaling Long-distance signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Endocrine cell Blood vessel Neurotransmitter diffuses across synapse Secreting cell Secretory vesicle Hormone travels in bloodstream to target cells Local regulator diffuses through extracellular fluid Target cell Target cell is stimulated Paracrine signaling Synaptic signaling Hormonal signaling

The Three Stages of Cell Signaling Reception Transduction Response

Reception The binding between a signal molecule (ligand) and receptor is highly specific A conformational change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins EXTRACELLULAR FLUID Reception Plasma membrane Transduction CYTOPLASM Receptor Signal molecule

Relay molecules in a signal transduction Usually involves multiple steps Multistep pathways can amplify a signal EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Transduction Receptor Relay molecules in a signal transduction pathway Signal molecule

Relay molecules in a signal transduction Response Signal transduction pathways lead to regulation of one or more cellular activities EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Transduction Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule

Intracellular Receptors Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers (lipid steroids) can readily cross the membrane and activate receptors An activated hormone-receptor complex can act as a transcription factor, turning on specific genes

Hormone (testosterone) EXTRACELLULAR FLUID The steroid hormone testosterone passes through the plasma membrane. Plasma membrane Testosterone binds to a receptor protein in the cytoplasm, activating it. Receptor protein Hormone- receptor complex The hormone- receptor complex enters the nucleus and binds to specific genes. DNA mRNA The bound protein stimulates the transcription of the gene into mRNA. NUCLEUS New protein The mRNA is translated into a specific protein. CYTOPLASM

Receptors in the Plasma Membrane Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane There are three main types of membrane receptors: G-protein-linked receptors Receptor tyrosine kinases Ion channel receptors

G-Protein-Linked Receptor A G-protein-linked receptor is a plasma membrane receptor that works with the help of a G protein The G-protein acts as an on/off switch: GTP= active GDP= inactive Signal-binding site Segment that interacts with G proteins

First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein G-protein-linked receptor GTP ATP Second messenger cAMP Protein kinase A Cellular responses

Ion Channel Receptor Acts as a gate when the receptor changes shape Signal molecule (ligand) Gate closed Ions Acts as a gate when the receptor changes shape Plasma membrane Ligand-gated ion channel receptor Gate open Cellular response Gate closed

Signal Transduction Pathways The molecules that relay a signal from receptor to response are mostly proteins Behave similar to falling dominos At each step, the signal is transduced into a different form, usually a conformational change EXTRACELLULAR FLUID Reception Plasma membrane Transduction CYTOPLASM Receptor Signal molecule Relay molecules in a signal transduction pathway Response Activation of cellular response

Protein Phosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a cascade of protein phosphorylations Phosphatase enzymes remove the phosphates This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off

Phosphorylation cascade Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Active protein kinase 2 P Phosphorylation cascade PP P i Inactive protein kinase 3 ATP ADP Active protein kinase 3 P PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i

Small Molecules and Ions as Second Messengers Second messengers are small, nonprotein, water-soluble molecules or ions The extracellular signal molecule that binds to the membrane is a pathway’s “first messenger” Second messengers can readily spread throughout cells by diffusion Second messengers participate in pathways initiated by G-protein-linked receptors and receptor tyrosine kinases

Cyclic AMP Cyclic AMP (cAMP) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal Adenylyl cyclase Phosphodiesterase Pyrophosphate H2O P P i ATP Cyclic AMP AMP

First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein G-protein-linked receptor GTP ATP Second messenger cAMP Protein kinase A Cellular responses

Cytoplasmic and Nuclear Responses Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the cytoplasm or may involve action in the nucleus Many pathways regulate the activity of enzymes

Note the amplification Reception Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Note the amplification Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules)

Cytoplasmic and Nuclear Responses Many other signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus The final activated molecule may function as a transcription factor

Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Response P DNA Gene NUCLEUS mRNA