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 Cell junctions Plasmodesmata between plant cells 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 Secreting cell Secretory vesicle Neurotransmitter diffuses across synapse Hormone travels in bloodstream to target cells Local regulator diffuses through extracellular fluid Paracrine signaling Target cell is stimulated Synaptic signaling Target cell 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 Receptor Reception Plasma membrane Transduction CYTOPLASM Signal molecule
Transduction Usually involves multiple steps Multistep pathways can amplify a signal EXTRACELLULAR FLUID Receptor Reception Plasma membrane Transduction CYTOPLASM Relay molecules in a signal transduction pathway Signal molecule
Response Signal transduction pathways lead to regulation of one or more cellular activities EXTRACELLULAR FLUID Plasma membrane CYTOPLASM Reception Transduction Response Receptor Relay molecules in a signal transduction pathway Activation of cellular response 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) Receptor protein EXTRACELLULAR FLUID Plasma membrane Hormonereceptor complex The steroid hormone testosterone passes through the plasma membrane. Testosterone binds to a receptor protein in the cytoplasm, activating it. mrna NUCLEUS CYTOPLASM DNA New protein The hormonereceptor complex enters the nucleus and binds to specific genes. The bound protein stimulates the transcription of the gene into mrna. The mrna is translated into a specific protein.
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) G protein Adenylyl cyclase G-protein-linked receptor GTP ATP camp Second messenger Protein kinase A Cellular responses
Ion Channel Receptor Acts as a gate when the receptor changes shape Signal molecule (ligand) Gate closed Ligand-gated ion channel receptor Gate open Ions Plasma membrane 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 Receptor Signal molecule Reception Plasma membrane Transduction CYTOPLASM 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
Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase ATP 2 ADP Active protein P i PP kinase 2 P Inactive protein kinase ATP ADP 3 Active protein P i PP kinase 3 P Inactive protein P i ATP PP ADP Active protein P Cellular response
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 P P i H 2 O ATP Cyclic AMP AMP
First messenger (signal molecule such as epinephrine) G protein Adenylyl cyclase G-protein-linked receptor GTP ATP camp Second messenger 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
Reception Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Note the amplification 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 ) Response Glycogen Glucose-1-phosphate (10 8 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 Receptor Reception Phosphorylation cascade Transduction CYTOPLASM DNA Inactive transcription factor Active transcription factor P Response Gene NUCLEUS mrna