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Modes of Protein Transport
Nuclear pores
Translocators (organelles)
Vesicles (everywhere else)
Protein Localization
Determined by amino acid sequence
Altering signal sequence changes localization
Nuclear Pores
Multi-protein complexes spanning nuclear envelope
Nuclear Pore Structure
Cytosolic fibrils: bind nuclear import proteins
Intrinsically disordered fibers: prevent random diffusion
Nuclear Import Process
Nuclear import receptors recognize cargo in cytosol
Receptors & cargo wiggle through nuclear pore fibers
Inside nucleus, cargo is released
Nuclear Export
Similar to import but moves molecules (e.g., mRNA) out
Ran G Protein Cycle
Ran-GTP: inside nucleus, releases cargo
Ran-GDP: in cytosol, binds import receptors for return
Ran Regulation
Ran-GEF (nucleus): promotes Ran-GTP
Ran-GAP (cytosol): converts Ran-GTP to Ran-GDP
Mitochondrial & Chloroplast Protein Transport
Proteins translated in cytosol
Threaded into organelles via translocators
Peroxisome Protein Transport
Direct transport & ER shuttling by vesicles
Endoplasmic Reticulum (ER)
Largest membrane system in the cell
Ribosome Pool
Free vs. membrane-bound depends on the protein being synthesized
ER Signal Sequence
Pauses translation
Ribosome docks at ER membrane via signal-recognition particle (SRP)
Soluble ER Proteins
Fully translocated into ER lumen
Signal sequence is cleaved
Single-Pass Transmembrane Proteins
Stop-transfer sequence locks protein in membrane
Multi-Pass Transmembrane Proteins
Internal signal sequences & stop-transfer sequences create multiple domains
Vesicle Transport
Vesicles originate & fuse with membranes for transport
Clathrin-Coated Vesicles
Clathrin triskelions form basket-like structures
Cargo Selection for Vesicles
Clathrin attaches to cargo receptors via adaptins
ER Size Regulation
Based on demand for secretory & membrane proteins
Protein Glycosylation in ER
N-glycosylation: Sugar chains added to asparagine residues
ER Quality Control
Misfolded proteins retained in ER
Calnexin helps proper folding
ER Stress & Apoptosis
Accumulated misfolded proteins cause ER swelling → cell death
Golgi Apparatus Function
Protein modification & sorting center
Cis-face: receives vesicles
Trans-face: ships vesicles
Exocytosis Types
Constitutive: Continuous release
Regulated: Signal-dependent release
Neurotransmitter Secretion
Voltage-gated calcium channels trigger vesicle fusion
Endocytosis Types
Phagocytosis: Engulfs large particles (macrophages, neutrophils)
Receptor-mediated endocytosis
Pinocytosis: Exploited by viruses
Endocytosis Receptor Fates
Recycling (returns to plasma membrane)
Degradation (lysosome breakdown)
Transcytosis (transport across the cell)
Lysosomal Digestion
Acidic pH maintained by ATP-powered proton pump
Metabolites exit lysosome via transporters
Lysosome Pathways
Phagocytosis, Endocytosis, Autophagy