Cell Biology Study Guide: Endomembrane System, Signaling, Cytoskeleton, Cell Movement, Junctions, and Extracellular Matrix

Endomembranes and Trafficking

Endomembrane System Components

The endomembrane system is a network of membranous organelles within eukaryotic cells that coordinates the synthesis, processing, and transport of proteins and lipids.

• Endoplasmic Reticulum (ER):

  • Rough ER: Studded with ribosomes; site of protein synthesis and initial folding.

  • Smooth ER: Functions in drug detoxification, carbohydrate metabolism, calcium storage, and steroid biosynthesis.

• Golgi Apparatus: Consists of cis (entry) and trans (exit) sides; processes, sorts, and traffics proteins and lipids.

• Lysosome: Degrades macromolecules; develops from endosomes; contains acidic environment for hydrolytic enzymes.

Trafficking Between Compartments

Cellular trafficking involves the transport of proteins and biomolecules between endomembrane compartments via vesicles.

• Directionality:

  • Anterograde: ER → Golgi → plasma membrane/lysosome

  • Retrograde: Golgi → ER

• Cotranslational Import: Proteins with signal sequences are recognized by the signal recognition particle (SRP) and imported into the ER via the translocon. Folding and processing occur in the ER.

• Integral Membrane Protein Insertion: Stop-transfer and start-transfer sequences guide insertion into the ER membrane.

• Posttranslational Import: Proteins imported after translation, often into organelles like mitochondria.

• Protein Sorting: Retention and retrieval tags (amino acid sequences, hydrophobic region length, covalent modifications) ensure correct localization.

Exocytosis and Endocytosis

• Exocytosis: Process by which vesicles fuse with the plasma membrane to secrete contents. Types include constitutive and regulated secretion.

• Endocytosis: Uptake of external materials via vesicle formation.

  • Types: Phagocytosis, pinocytosis, receptor-mediated endocytosis.

  • Receptor-Mediated Endocytosis: Involves clathrin, adaptor proteins, and dynamin; steps include ligand binding, vesicle formation, and internalization. Fates include recycling or degradation of ligands/receptors.

Coated Vesicles

Coated vesicles facilitate transport between organelles, each with specific coat proteins:

Coat Protein	Origin Membrane	Destination Membrane
Clathrin	Plasma membrane, trans-Golgi	Endosomes, lysosomes
COPI	Golgi	ER (retrograde)
COPII	ER	Golgi (anterograde)

SNARE-Mediated Membrane Fusion

Membrane fusion is mediated by SNARE proteins and associated factors:

• v-SNAREs: Located on vesicles

• t-SNAREs: Located on target membranes

• Tethering Proteins: Facilitate initial contact

• Rab GTPases: Regulate vesicle targeting

• NSF and SNAPs: Mediate SNARE complex disassembly

• Steps: Tethering → docking → fusion → release of cargo

Signaling Transduction – Electrical and Synaptic

Cell Types of the Nervous System

• Neurons: Sensory, motor, and interneurons; transmit electrical signals.

• Glial Cells: Microglia (immune), oligodendrocytes (CNS myelination), Schwann cells (PNS myelination), astrocytes (support and regulation).

Neuron Morphology and Function

• Structure: Dendrites (input), cell body (integration), axon (output), synaptic terminals (signal transmission).

• Synapse: Junction between neurons for signal transmission.

Membrane Potential and Ion Movement

• Resting Potential: Maintained by Na+/K+ pumps; typically -70 mV.

• Action Potential:

  • Depolarization: Na+ influx

  • Repolarization: K+ efflux

  • Hyperpolarization: Excess K+ outflow

Electrical Signal Transmission

• Nonmyelinated Axons: Continuous conduction

• Myelinated Axons: Saltatory conduction (nodes of Ranvier)

• Synaptic Transmission:

  • Chemical Synapses: Neurotransmitter release and uptake

  • Electrical Synapses: Direct ion flow via gap junctions

Signaling Transduction – Chemical

Key Terms and Concepts

• Receptors: Proteins that bind ligands to initiate signaling

• Ligands: Signaling molecules

• Agonists/Antagonists: Activate or inhibit receptors

• Second Messengers: Intracellular signaling molecules (e.g., cAMP, Ca2+)

• Signal Amplification: Cascade increases response magnitude

GPCR Pathway

• GPCRs: Seven transmembrane domain proteins; activate heterotrimeric G proteins (Gα, Gβ, Gγ)

• G Proteins: "On" with GTP, "off" with GDP

• Downstream Signaling:

  • Gsα: Activates adenylyl cyclase → cAMP → protein kinase A (PKA)

  • Gqα: Activates phospholipase C (PLC) → IP3 and DAG; IP3 increases cytosolic Ca2+ via ER channels

Receptor Tyrosine Kinase (RTK) Pathway

• RTK Structure: Extracellular ligand-binding domain, transmembrane region, intracellular tyrosine kinase domain

• Signaling Cascade: Ligand binding → receptor dimerization → autophosphorylation → adaptor protein recruitment → Ras activation → MAP kinase cascade → gene expression

• Alternative Pathways: RTK activation can also stimulate PLC and PI3K

Signal Integration and Crosstalk

• Multiple pathways can interact and modulate cellular responses.

• Signals can be short-range (local) or long-range (hormonal).

• Hormones may act via nuclear receptors to regulate gene expression.

Cytoskeletons

Types and Cellular Roles

The cytoskeleton provides structural support, facilitates movement, and organizes cellular components.

• Microtubules (MTs): Tubulin subunits; cytoplasmic (cell shape, transport) and axonemal (cilia/flagella) types

• Microfilaments (Actin Filaments): Actin subunits; cell shape, motility, muscle contraction

• Intermediate Filaments: Diverse proteins (keratins, lamins); mechanical strength

Microtubules

• Assembly: Requires GTP; exhibits polarity (plus and minus ends)

• Treadmilling: Dynamic addition/removal of subunits

• Dynamic Instability: Alternates between growth (rescue) and shrinkage (catastrophe)

• MTOCs: Centrosomes and basal bodies; gamma-tubulin nucleates MTs

Microfilaments (Actin Filaments)

• Assembly: Requires ATP; exhibits polarity

• Structures: Stress fibers, gel-like networks, branched (lamellipodia), parallel (filopodia)

• Branching Proteins: Arp2/3 complex, Rho family GTPases

Intermediate Filaments

• Subunits: Keratins (epithelial), lamins (nuclear envelope)

• Assembly: No energy requirement; nonpolar

Cell Movement

Motor Proteins

• Kinesins: Move toward MT plus end; use ATP

• Dyneins: Move toward MT minus end; use ATP

• Cilia/Flagella Motion: Dynein-mediated sliding of MTs produces movement

Actin-Based Movement

• Myosins: Motor proteins that move along actin filaments

• Muscle Contraction: Thick (myosin) and thin (actin) filaments form sarcomeres; contraction via sliding-filament model

• Regulation: Troponin, tropomyosin, and Ca2+ ions control contraction

• Nonmuscle Motility: Actin-myosin interactions drive cell movement

Cell-Cell Junctions

Major Types

• Adhesive Junctions:

  • Adherens Junctions: Cadherin proteins; connect actin filaments

  • Desmosomes: Desmoglein/desmocollin; connect intermediate filaments

• Tight Junctions: Seal spaces between cells; claudins and occludins

• Gap Junctions: Allow ion and molecule passage; connexin proteins

• Plasmodesmata (plants): Channels for cell-cell communication

Extracellular Matrix (ECM)

Major ECM Proteins

• Collagens: Provide tensile strength

• Elastins: Confer elasticity

• Proteoglycans: Hydration and cushioning

• Fibronectins: Cell adhesion and migration

• Laminins: Basal lamina structure and cell attachment

Basal Lamina and Cell-ECM Adhesion

• Basal Lamina: Specialized ECM layer under epithelial cells

• Focal Junctions: Integrin-mediated cell-ECM adhesion

• Hemidesmosomes: Anchor cells to basal lamina