Receptor

Molecule allowing a cell to recognize a message and respond to it

Ligand

Molecule that specifically binds to another molecule

Cell Junctions

• Local signaling
• Use gap junctions
• Signals can bypass cell membrane

Direct Contact

• Local signaling
• Requires cell to cell contact
• Signal molecule bound on cell membrane
• Signal molecule on one cell binds to receptor molecule on another cell

Paracrine

• Local signaling
• Cell releases soluble signal molecules into the extracellular space
• Signals diffuse from releasing cell and reach target cell

Synaptic

• Local signaling
• Allows neurons to pass signals to other cells
• Use neurotransmitters as signal molecules

Endocrine

• Long distance signaling
• Signals travel through blood vessels before reaching target cell
• Insulin released by pancreas into bloodstream causes cells all over the body to absorb glucose from the bloodstream

• Programmed cell death
• Specific biochemical signature (ex. phosphatidylserine “flips” to outer surface of plasma membrane)
• Does not induce inflammation

Important in a Variety of Processes

• Organism development
• Cell number and organ size
• Quality control during development
• Removal of damaged cells

Cellular Changes

• Cytoplasm condenses
• Nucleus becomes misshapen
• Chromatin condenses along the nuclear envelope
• Cell eventually fragments into blebs
• Phosphatidylserine on the blebs indicates to phagocytic cells that apoptosis is occurring
• Phagocytic cells clear the cellular debris

Two Paths of Apoptosis

1. Extrinsic Pathway (using the Fas pathway as an example)

a) Trimeric Fas ligand on another cell binds to Fas death receptor
b) Intracellular domain of Fas receptor recruits and activates FADD (Fas associated death domain)
c) Activated FADD recruits initiator procaspases such as procaspase-8 or -10 (complex is referred to as death-inducing signaling complex or DISC)
d) Complex formation activates the procaspases which then activate executioner caspases
e) Executioner caspase activation leads to apoptosis

2. Intrinsic Pathway

a) Apoptotic stimulus activates BH3-only protein
b) BH3-only protein blocks the activity of Bcl-2 protein
c) Without Bcl-2 activity, BH123 proteins are able to oligomerize and cytochrome c is released from the intermembrane space of mitochondria
d) Cytochrome c in the cytoplasm activates Apaf1 proteins which form a heptameric complex
e) Apaf1 complex recruits initiator procaspase-9
f) Activated caspase-9 activates executioner caspase
g) Executioner caspase activation leads to apoptosis

Bcl-2 Family of Proteins

• Based on which specific domains are present in the protein

1. Anti-apoptotic Bcl-2 proteins (ex. Bcl-2 or Bcl-XL)
2. Pro-apoptotic BH123 proteins (ex. Bax or Bak)
3. Pro-apoptotic BH-3 proteins

PLASMA MEMBRANE

• Often called phospholipid bilayer
• Comprises: Proteins, Cholesterol, Carbohydrates.
• Separates cell from external environment; controls the flow of material into and out of it.

CYTOSOL

• Aqueous solution that bathes organelles and contains a variety of molecules
• Portion of cytoplasm not contained within organelles
• Free ribosomes

ENDOMEMBRANE SYSTEM

• Select group of membranous organelles that regulate protein trafficking and metabolism

NUCLEUS

• Nuclear envelope with pores (double-membrane)
• Site of DNA replication and RNA synthesis (transcription)
• Contains: chromatin, nucleolus (rRNA and ribosomal proteins)

ENDOPLASMIC RETICULUM

• Continuous with nuclear envelope
• Cisternae enclose a space called the ER lumen
• Rough ER: with bound ribosomes; site of protein synthesis, processing and secretion
• Smooth ER: no ribosomes; lipid synthesis, carbohydrate metabolism, detoxification

TRANSPORT VESICLE

• Keeps secretory proteins separate from proteins synthesized in the cytosol

GOLGI APPARATUS

• cis side faces the nucleus, trans side where cargo exits
• Modifies, stores and secretes molecules that it receives from the ER
• Synthesizes its own macromolecules

LYSOSOME

• Vesicle that contains hydrolytic enzymes; digests endosomal cargo

ENDOSOME

• Forms when cell engulfs nutrients or other particles via endocytosis

RIBOSOMES

• Two subunits: one large and one small
• Synthesize proteins via translation
• Can be bound to rough ER or free (suspended in cytosol)

MITOCHONDRION

• Double-membrane bound: inner membrane invaginates to form cristae
• Space within cristae: matrix (contains free ribosomes)
• Space between inner and outer membranes: intermembrane space
• Synthesizes ATP via citric acid cycle and oxidative phosphorylation (couples oxidation of nutrients with ADP phosphorylation)

PEROXISOME

• Single-membrane bound vesicle
• Produce hydrogen peroxide from detoxification of substances (i.e. alcohol)

CYTOSKELETON

• Microfilaments, intermediate filaments and microtubules
• Anchors organelles and provides structural framework

CENTROSOME

• Where microtubules nucleate
• Contains two small structure called centrioles
• Functions in cell division

DOUBLE MEMBRANE BOUND ORGANELLES

• Nucleus
• Mitochondria

CLINICAL CORRELATIONS

• Rough ER Network and Pancreatic beta cells
  – Specialize in synthesizing and secreting the peptide hormone insulin; large rough ER network proportional to their secretory activity
• Smooth ER and Hepatic cells
  – Drugs and/or alcohol can induce the proliferation of smooth ER, which accelerates detoxification
• Lysosomes and Tay-Sachs disease
  – Lysosomal storage disease that presents when lysosomes are missing a lipid-digesting enzyme (or its active form)
  – Lipids accumulate in cells because lysosomes cannot digest them; impair brain function

SOURCE – CARANZZA TEXTBOOK

SOURCE – CARANZZA TEXTBOOK