Protein Sorting Flashcards
What is the nature of nuclear localization signals (NLS)?
Short amino acid sequences that direct proteins to the nucleus, typically rich in basic residues (e.g., lysine, arginine).
What is the function of nuclear pores?
Large protein complexes that allow selective transport of molecules between the nucleus and cytoplasm.
What soluble factors are involved in nuclear import?
Importins (karyopherins), Ran-GTP, and NTF2 facilitate nuclear import by recognizing NLS and regulating transport through the pore.
How does Ran-GTP regulate nuclear import?
Ran-GTP binds importin in the nucleus, causing cargo release, while Ran-GDP in the cytoplasm promotes importin-cargo binding.
What are mitochondrial targeting signals (MTS)?
Amphipathic alpha-helical sequences at the N-terminus of proteins destined for mitochondria.
How are proteins sorted to different mitochondrial compartments?
Additional sorting signals (e.g., TIM/TOM complexes) direct proteins to the matrix, inner membrane, outer membrane, or intermembrane space.
What is the signal sequence for ER targeting?
A hydrophobic N-terminal sequence recognized by the signal recognition particle (SRP).
How does protein translocation into the ER occur?
Via the Sec61 translocon, which allows polypeptide chains to cross or integrate into the ER membrane.
What post-translational modifications occur in the ER?
N-glycosylation, disulfide bond formation, and GPI-anchor addition.
What is ER quality control?
Chaperones (e.g., BiP) and folding enzymes ensure proper protein folding; misfolded proteins are degraded via ERAD (ER-associated degradation).
What drives vesicle formation in the secretory pathway?
Coat proteins (COPII for ER→Golgi, COPI for retrograde) and GTPases (e.g., Sar1, ARF) deform membranes into vesicles.
How are transport vesicles targeted to the correct membrane?
Rab GTPases and t-SNAREs on target membranes bind v-SNAREs on vesicles to ensure specific docking/fusion.
What is receptor-mediated endocytosis?
Clathrin-coated pits internalize specific ligands (e.g., LDL) bound to receptors via adaptor proteins (e.g., AP2).
How does ubiquitin regulate receptor downregulation?
Ubiquitin tags receptors for endocytosis and lysosomal degradation, reducing cell surface levels (e.g., EGFR signaling attenuation).
What is the role of the TOM complex in mitochondrial protein import?
Translocase of the Outer Membrane (TOM) imports all nucleus-encoded mitochondrial proteins across the outer membrane.
What is the role of the TIM complex in mitochondrial protein import?
Translocase of the Inner Membrane (TIM) sorts proteins to the matrix or inner membrane using membrane potential.
What is the function of the signal recognition particle (SRP) in ER targeting?
SRP binds the ER signal sequence, pauses translation, and delivers the ribosome to the SRP receptor on the ER membrane.
What is the unfolded protein response (UPR)?
A stress pathway activated by misfolded ER proteins, increasing chaperone production or triggering apoptosis if overloaded.
What are the main types of vesicle coats in the secretory pathway?
COPII (anterograde ER→Golgi), COPI (retrograde Golgi→ER), and clathrin (Golgi→lysosomes/endosomes/plasma membrane).
How do SNARE proteins mediate vesicle fusion?
v-SNAREs on vesicles and t-SNAREs on target membranes form a tight complex that pulls membranes together for fusion.
What is the difference between constitutive and regulated secretion?
Constitutive secretion is continuous; regulated secretion (e.g., hormones) stores cargo in vesicles until a signal triggers release.
What is phagocytosis?
Uptake of large particles (e.g., bacteria) via actin-driven membrane protrusions, distinct from clathrin-mediated endocytosis.
What is pinocytosis?
Non-specific uptake of extracellular fluid and small molecules via small vesicles (bulk endocytosis).
How does dynamin function in endocytosis?
A GTPase that pinches off clathrin-coated vesicles from the plasma membrane by constricting the vesicle neck.