16.1: Overview of Protein Sorting and Transport

Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.

Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded proteins with exposed nuclear localization signals are recognized by soluble cytosolic receptors. The cytosolic receptor binds the cargo and transports it across the nucleus by passing through the nuclear pore complex embedded in the nuclear membrane.

In contrast, precursors of proteins are translocated or moved from the cytosol to different organelles such as mitochondria, chloroplast, Endoplasmic Reticulum (ER), and peroxisomes. During protein translocation, cytosolic chaperones bind and unfold the target protein to guide them to the organelle surface. Specific receptors on an organelle membrane recognize the signal sequences on the unfolded protein precursor and bind them. The unfolded peptide chain is threaded through specialized transporters called translocons to cross the lipid bilayer membrane and reach the lumen of the organelle.

Protein sorting by vesicular trafficking involves the movement of proteins in membrane-bound structures called transport vesicles. Soluble proteins in the ER lumen get packed onto the transport vesicles and are bud off from the ER membrane. Molecular markers displayed on the organelle membrane guide the proper delivery and fusion of the transport vesicles.

Protein sorting occurs during translation or after protein synthesis by two distinct processes: signal-based sorting and vesicle-based trafficking. Signal-based sorting employs two modes of transport: gated transport and protein translocation.

Nuclear proteins are actively transported from the cytosol to the nucleus via the nuclear pore complexes embedded in the nuclear envelope. This process is called gated transport.

These proteins contain specific amino acid sequences called sorting signals that are recognized by a sorting receptor that transports the protein to the nucleus.

Proteins targeted to the chloroplasts, mitochondria, and endoplasmic reticulum are imported through translocons, specialized transmembrane proteins, in a process called protein translocation.

During translocation, chaperone proteins in the cytosol bind to the target protein and deliver it to the membrane, where the sorting signals are recognized by the import receptors of the translocon. Using ATP hydrolysis, the target protein is unfolded and transported through a channel in the translocon to reach its destination within the organelle.

In vesicular trafficking, soluble proteins are packed from the endoplasmic reticulum lumen and loaded onto membrane-bound transport vesicles.

Transport vesicles bud off from the endoplasmic reticulum membrane and fuse with the Golgi membrane or the cell membrane without crossing the lipid bilayers to deliver the proteins to their target location.