Cell Biology Study Guide: Endomembrane System, Signaling, Cytoskeleton, Cell Movement, and Cell Interactions

Endomembranes and Trafficking

Endomembrane System Components: Morphology and Functions

The endomembrane system is a network of membrane-bound organelles within eukaryotic cells that coordinate the synthesis, modification, and transport of proteins and lipids.

• Endoplasmic Reticulum (ER):

  • Rough ER: Studded with ribosomes; site of protein synthesis for secretory and membrane proteins.

  • Smooth ER: Lacks ribosomes; involved in drug detoxification, carbohydrate metabolism, calcium storage, and steroid biosynthesis.

• Golgi Apparatus: Consists of cis (entry) and trans (exit) faces; responsible for processing, sorting, and trafficking of proteins and lipids.

• Lysosomes: Acidic organelles that degrade macromolecules; develop from endosomes.

Trafficking Between Endomembrane Compartments

Cellular trafficking involves the movement of proteins and other biomolecules between organelles via vesicles.

• Directionality:

  • Anterograde transport: From ER → Golgi → plasma membrane/lysosome.

  • Retrograde transport: From plasma membrane/Golgi → ER.

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

• Integral Membrane Protein Insertion: Uses stop-transfer and start-transfer sequences to embed proteins in the ER membrane.

• Posttranslational Import: Some proteins are imported into organelles after translation.

• Protein Sorting: Involves retention and retrieval tags (amino acid sequences, hydrophobic region length, covalent modifications) to direct proteins to correct locations.

Exocytosis and Endocytosis

• Exocytosis: Process by which vesicles fuse with the plasma membrane to secrete contents. Types include constitutive (continuous) and regulated (stimulus-dependent) secretion.

• Endocytosis: Uptake of external materials via vesicle formation.

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

  • Receptor-mediated endocytosis: Involves clathrin (coat protein), adaptor proteins, and dynamin (GTPase for vesicle scission). Ligands and receptors are internalized and sorted for recycling or degradation.

Coated Vesicles

Vesicles are coated with specific proteins that determine their origin and destination.

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

SNARE-Mediated Membrane Fusion

Vesicle fusion with target membranes is mediated by SNARE proteins and associated factors.

• v-SNAREs: Located on vesicles.

• t-SNAREs: Located on target membranes.

• Tethering proteins and Rab GTPases ensure specificity.

• NSF and SNAPs mediate SNARE complex disassembly after fusion.

• Steps: Tethering → Docking → Fusion → Disassembly.

Signal Transduction – Electrical and Synaptic

Cell Types of the Nervous System

• Neurons: Specialized for signal transmission; types include sensory, motor, and interneurons.

• Glial Cells: Support neurons; types include microglia, oligodendrocytes, Schwann cells, and astrocytes.

Neuron Morphology and Function

• Cell body (soma): Contains nucleus and organelles.

• Dendrites: Receive signals.

• Axon: Transmits signals to other cells.

Synapse and Membrane Potential

• Synapse: Junction where neurons communicate with other cells.

• Resting Potential: The membrane potential of a neuron at rest, typically around -70 mV.

• Action Potential: Rapid change in membrane potential due to Na+ influx (depolarization), followed by K+ efflux (repolarization and hyperpolarization).

Electrical Signal Transmission

• Nonmyelinated Axons: Action potential propagates continuously along the axon.

• Myelinated Axons: Action potential jumps between nodes of Ranvier (saltatory conduction), increasing speed.

Signal Transmission at Synapses

• Chemical Synapses: Neurotransmitters are released from presynaptic neuron and bind to receptors on postsynaptic cell.

• Electrical Synapses: Direct passage of ions via gap junctions.

• Neurotransmitter Uptake: Removal from synaptic cleft by reuptake or enzymatic degradation.

Signal Transduction – Chemical

Key Terms and Concepts

• Receptors: Proteins that bind signaling molecules (ligands).

• Ligands: Molecules that bind to receptors to initiate signaling.

• Agonists: Activate receptors; Antagonists: Block receptor activity.

• Second Messengers: Small molecules (e.g., cAMP, Ca2+) that relay signals inside the cell.

• Signal Amplification: One ligand can activate many downstream molecules via a signaling cascade.

G Protein-Coupled Receptor (GPCR) Pathway

• GPCRs: 7-transmembrane domain receptors; bind extracellular ligands.

• G Proteins: Heterotrimeric (Gα, Gβ, Gγ); active when bound to GTP, inactive with GDP.

• Downstream Signaling:

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

  • Gqα: Activates phospholipase C (PLC) → produces IP3 and DAG; IP3 releases Ca2+ from ER, leading to calcium signaling.

Receptor Tyrosine Kinase (RTK) Pathway

• RTKs: Single-pass transmembrane proteins with intrinsic tyrosine kinase activity.

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

• Alternative pathways: RTK activation can also stimulate PLC and PI3K.

Signal Integration and Crosstalk

• Cells integrate multiple signals; pathways can interact (crosstalk) to modulate responses.

Short- vs. Long-Range Signals

• Short-range: Paracrine, synaptic.

• Long-range: Endocrine (hormones).

Hormones and Nuclear Receptors

• Hormones: Chemical messengers that travel through the bloodstream.

• Nuclear Receptors: Intracellular receptors that regulate gene expression upon ligand binding.

Cytoskeletons

Types and Cellular Roles

The cytoskeleton provides structural support, facilitates cell movement, and organizes organelles.

• Microtubules (MTs): Hollow tubes; roles in cell shape, transport, and division.

• Microfilaments (Actin Filaments): Thin, flexible fibers; roles in cell movement and shape.

• Intermediate Filaments: Rope-like fibers; provide mechanical strength.

Microtubules

• Types: Cytoplasmic (cell shape, transport) and axonemal (cilia, flagella).

• Subunit: α- and β-tubulin dimers.

• Assembly: GTP-dependent polymerization; exhibits polarity (plus and minus ends).

• Treadmilling: Addition at plus end, loss at minus end.

• Dynamic Instability: Alternating growth and shrinkage (catastrophe and rescue).

• MTOCs: Microtubule-organizing centers (centrosome, basal bodies); contain γ-tubulin.

Microfilaments (Actin Filaments)

• Subunit: Globular actin (G-actin) polymerizes to form filamentous actin (F-actin).

• Assembly: ATP-dependent; exhibits polarity.

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

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

Intermediate Filaments

• Subunits: Diverse (e.g., keratins, lamins).

• Assembly: No energy required; non-polar.

Cell Movement

Motor Proteins

• Microtubule-based:

  • Kinesins: Move toward plus end; use ATP.

  • Dyneins: Move toward minus end; use ATP.

• Cilia/Flagella Motion: Dynein-mediated sliding of microtubules causes bending and movement.

• Actin-based: Myosins move along actin filaments using ATP.

Muscle Contraction

• Thick filaments: Myosin; Thin filaments: Actin.

• Sarcomere: Functional unit of muscle contraction.

• Sliding-Filament Model: Myosin heads bind actin, hydrolyze ATP, and "walk" along actin, shortening the sarcomere.

• Regulation: Troponin and tropomyosin block or expose binding sites in response to Ca2+ levels.

Nonmuscle Motility

• Actin and myosin interactions drive cell crawling, cytokinesis, and vesicle transport.

Cell-Cell Junctions

Major Types and Features

• Adhesive Junctions:

  • Adherens Junctions: Connect actin cytoskeletons of adjacent cells via cadherins.

  • Desmosomes: Connect intermediate filaments via desmogleins and desmocollins.

• Tight Junctions: Seal spaces between cells; prevent paracellular transport.

• Gap Junctions: Allow direct passage of ions and small molecules between cells.

• Plasmodesmata (plants): Channels for communication between plant cells.

Extracellular Matrix (ECM)

Major Components

• Collagens: Provide tensile strength.

• Elastins: Provide elasticity.

• Proteoglycans: Hydrated gel; resist compression.

• Fibronectins and Laminins: Mediate cell adhesion and migration.

Basal Lamina

• Specialized ECM layer underlying epithelial cells; provides support and filtration.

Cell-ECM Adhesion

• Focal Junctions: Link actin cytoskeleton to ECM via integrins.

• Hemidesmosomes: Link intermediate filaments to ECM.