Receptors and Cell Signaling

Learning Objectives

• Describe general steps of intercellular signalling

• Different types of cell signals

• Distinguish between endocrine, paracrine, and autocrine signalling

• Discuss intracellular signalling systems and the role of second messengers

Membrane Proteins

• Functions of membrane proteins:

  • Transport proteins

  • Enzymes

  • Intercellular junctions

  • Cell-cell recognition

  • Receptors

  • Adhesion to extracellular matrix

Membrane Receptors

• Mechanism:

  • Bind the signal or ligand

  • Produce a second signal/second messenger

  • Cause cellular response

  • Some signals can cross the membrane

Importance of Cell Signalling

• Reasons cells need receptors and signalling systems:

  • Respond to changes in immediate environment

  • Enable cell communication

  • Coordinate cellular function control

  • Mediate intercellular and intracellular signalling

Intercellular Communication

• Process:

  1. Reception of triggering stimulus

  2. Transformation into a chemical/electrical messenger

  3. Messenger secretion and transport to target cell

  4. Recognition and conversion into a biochemical reaction in the target cell

Types of Signalling

• Direct Signalling:

  • Transfer of ions/small molecules directly between neighboring cells

  • Fastest mode of communication (e.g., heart, neurons)

  • Utilizes gap junctions:

  • Form hydrophilic channels that allow direct communication

  • Allows transfer of molecules like ATP, cAMP, and ions (e.g., $Ca^{2+}$)

• Endocrine Signalling:

  • Signal: Hormones produced by endocrine glands

  • Can be:

  • Lipophilic (e.g., progesterone, testosterone)

  • Hydrophilic (e.g., insulin, glucagon)

  • Mechanism: Travel through bloodstream to distant cells; surface or intracellular receptors involved

• Paracrine Signalling:

  • Signal: Similar to hormones; does not enter blood circulation

  • Rapidly destroyed by extracellular enzymes or bound to matrix

  • Target cells located nearby; signal gradient determines response

• Synaptic Signalling:

  • Specialized form of paracrine signalling occurring at synapses

  • Example: Communication between neurons and effectors

• Autocrine Signalling:

  • Signal: Secreted by the target cell itself (e.g., prostaglandins)

  • Distinguishes itself from endocrine and paracrine signalling

Cellular Response to Signals

• Process of Response:

  1. Receptor protein receives signal

  2. Undergoes conformational change

  3. Initiates biochemical reactions within the cell

  4. Signal transduction cascades amplify message

  5. Multiple intracellular signals may be triggered

  6. Can affect gene expression, cell shape, movement, metabolism, etc.

Types of Receptors

• Receptor Types include:

  • Ion-channel receptors

  • Ligand-gated channels

  • Receptors with enzymatic activity

  • G protein-coupled receptors (GPCRs)

G Protein-Coupled Receptors (GPCRs)

• Structure: Integral membrane protein with 7 transmembrane regions

• Function: Ligand binding activates G proteins leading to secondary messengers production

G Protein Mechanism

• Functioning:

  • Inactive state: $G_{ ext{α}}$ binds to GDP

  • Ligand binding stimulates receptor, releasing GDP

  • GTP binds to the empty site, causing dissociation of $β ext{γ}$ subunits

  • GTP hydrolyzed back to GDP, completing the cycle

GPCR Signalling System

• How it works:

  1. Ligand binds to GPCR, activating it

  2. Activates G protein

  3. G protein activates effector enzyme to produce second messengers

Intracellular Signaling and Second Messengers

• Second Messengers:

  • Relay information from first messengers (hormones/signal molecules)

  • Generate various responses in the cell

• Example - cAMP (cyclic AMP):

  • Responds to signals like adrenaline and glucagon

  • Synthesized by adenylyl cyclase regulated by G proteins

  • Activates protein kinase A which phosphorylates target proteins

• Calcium ions $Ca^{2+}$

  • Functions as an intracellular signal

  • Important for processes like muscle contraction, exocytosis, and mitosis

  • Regulated by pumps transporting it out of cells or into the endoplasmic reticulum (ER)