BIOL 201 - 7. Intracellular Protein Targeting

Signal Sequences

A continuous stretch of amino acids (15 - 60) that targets or sorts proteins to the correct location

• part of the protein’s primary sequence and is often removed after sorting

Nuclear Localization Signal (NLS)

A signal sequence that, when added to a protein, results in its transfer to the nucleus

• 8 - 30 amino acids with positively charged side groups

Non-secretory Pathways

Protein sorting pathways that involve the cytoplasm or intracellular organelles

• pathway goes to the nucleus and mitochondria

Secretory Pathway

A protein sorting pathway that involves endomembrane system organelles

• goes to the ER, Golgi, lysosome, and plasma membrane

• proteins are destined for secretion from the cell

Nuclear Transport

Transport that involves targeting sequences, transport proteins, and an energy source

Nuclear Pores

Pores that transport 500 macromolecules every second, in both directions at the same time

• created from nucleoporins

FG-nucleoporins (FG-nups)

Nucleoporins in the central channel that forms a barrier restricting the diffusion of other macromolecules

• contains long sequences of hydrophilic amino acids interspersed with cross linked hydrophobic FG-repeats

Nuclear Transporters

Receptors that bind to NLS on cargo and nuclear pore complex (NPC) proteins

• attaches to FG-repeats on FG nucleoporins found on the cytoplasmic fibrils of the NPC

• “importins” or “exportins”

Ran Proteins

G proteins involved in nuclear transport

GAPs (GTPase Activating Proteins)

Proteins that increase GTPase rate when GTP is bound to “ran”

GEFs (Guanine or GTP Exchange Factors)

Proteins that switch GDP for GTP on the “ran” protein

Localization of GEF and GAP in the cytosol

Ran-GAP converts Ran into GDP bound form (Ran-GDP)

Localization of GEF and GAP in the nucleus

Ran-GEF converts Ran into GTP bound form (Ran-GTP)

Nuclear Import

The process by which proteins are transported from the cytosol into the nucleus via NPCs

Mitochondrial Transport

Protein transport to the mitochondria, similar the nuclear transport, but proteins must be unfolded to cross mitochondrial membranes