Cell Signaling and Communication

Cell Signaling

• Cells respond to various stimuli
• External and internal signals affect cell structures, growth, reproduction, development, and behavior
• Protein receptors receive these signals
• Quorum sensing is coordinated behavior in bacteria at higher population densities via chemical signals leading to motility, antibiotic production, spore formation, or sexual conjugation.

Yeast Cell Communication

• Saccharomyces cerevisiae multiply by budding
• Cells send mating factors to stop budding and perform conjugation
• Diploid zygote formation allows genetic material combination and shuffling during spore formation.

Cell Communication in Multicellular Organisms

• Utilize chemical signals
• Receptive proteins (membrane or cytosolic) receive signals
• Intracellular signaling pathways or systems are activated by the binding of the signal to receptor
• Effector proteins including transcription factors, ion channels, metabolic enzymes, signaling proteins, and cytoskeletons are impacted
• Leads to changes in cell metabolism, gene expression, shape, or movement.

Cell-Surface Receptors (and intracellular)

• Extracellular signals are diverse (proteins, peptides, amino acids, nucleotides, steroids, retinoids, dissolved gases).
• Cell-surface receptors recognize mostly large, hydrophilic signals
• Intracellular receptors mostly recognize small, hydrophobic signals
• Signals are at low concentrations with high affinity to bind to receptors
• Ion-channel-coupled, G-protein-coupled, and enzyme-coupled receptors are described as different classes

Signaling by Phosphorylation

• Signal turns on or off
• Kinases add phosphate to proteins
• Phosphatases remove phosphate from proteins

Signaling by GTP Binding

• GTP binding proteins are responsible as the second messengers
• The protein is turned on when GTP is bound
• The protein is turned off when GTP is hydrolyzed to GDP.
• Two types: Trimeric and Monomeric GTP-binding proteins

Second Messengers as Molecular Switches

• Phosphorylation is the process of activating or deactivating second messengers
• Protein kinases add phosphate and protein phosphatases remove phosphate which controls second messenger function.

Intracellular Signaling Complexes

• Scaffold proteins group interacting signaling proteins to ensure efficiency, specificity, and robustness of the response
• Pre-assembled signal complex proteins
• Involved in signal pathways including activation of second messengers (phospholipids), complex assembly on scaffold proteins, and transient assembly of signal proteins following ligand binding.

Signaling Pathways

• Signal processing often involves a series of responses due to second messengers
• Signal integration is the ability of the cell to coordinate multiple inputs causing the effect to be the same even though multiple receptors are involved.
• Cell responses are the results of integrated signal pathways (two or more different signals bind to different receptors for a common response)

Signal Turnover

• Fast degrading signal molecules change their concentration quickly
• Slow degrading signal molecules change their concentration proportionally more slowly

Feedback Mechanisms

• Positive feedback results in outputs that perpetuate the signal, potentially causing an all-or-none response or bistable condition
• Negative feedback results in outputs that inhibit further signaling, potentially producing a brief, sustained, or oscillating response

G- Proteins (and GPCR Receptors)

• G-protein-coupled receptors (GPCRs) are the most common and diverse receptor type in terms of recognized signals (ligands).
• GPCRs have seven transmembrane domains
• Ligands are diverse; including hormones, neurotransmitters, light sensitive materials, and those with smell and taste
• Approximately 800 GPCRs are present in humans and over 1000 in mice.
• These receptors mediate variety of functions and ~half of all known drugs, bind to GPCRs

Cyclic AMP (cAMP) as Second Messenger

• CAMP is produced from ATP by adenyl cyclase.
• Activation of cAMP-dependent protein kinases is mediated by cAMP.
• cAMP-mediated effects can result in long term changes in cells.

G-proteins (Gs and Gi)

• Stimulatory G proteins (Gs) activate adenylyl cyclase and cAMP production.
• Inhibitory G proteins (Gi) inhibit adenylyl cyclase and suppress cAMP production.

Calcium Waves in Fertilized Eggs

• Fertilization triggers a wave of calcium release across the egg from the entry point of sperm
• Ca2+-induced Calcium Release (CICR) involves a positive feedback loop
• The wave of Ca2+ changes the egg surface preventing the entry of other sperm cells.

Calcium Signaling

• Calcium can serve as signal mediators in cells.
• Triggers muscle contraction, exocytosis, and other cellular processes
• The role of Calcium is mediated thru proteins such as calmodulin and kinases.

Intermediate Filaments

• Several types of intermediate filaments exist, each with specific functions and locations within the cell.
• They include lamins, neurofilaments, vimentin, desmin, and keratins.
• Mutations are associated with diseases.

Cell Migration

• Actin-rich cortex crucial
• Protrusion creation
• Attachment to substratum
• Traction which draws the rest of the cell forward is facilitated by forces from actin polymerization and myosin contraction.

Rac and Rho

• Rac GTPase promotes actin network formation and reduces myosin II activity
• Rho GTPase promotes more stress fiber formation and increases myosin II activity.