Protein Trafficking in Cell Biology - An Overview

Introduction

After the transcription (a process where RNA copy is made from a piece of DNA) and translation (process of making proteins with the help of messenger RNA) processes, the proteins need to be trafficked or directed to a certain location in the cell so that they can carry out their functions. These instructions are in the form of signal sequences, which are found mainly in the N-terminus of proteins and can also be found in the C-terminus or internal location of proteins.

What Is Protein Trafficking?

Protein trafficking is a process of transporting specific proteins into different organelles or nucleus with the help of signal peptides, which are a class of cleaved peptide sequences. These signal peptides or signal sequences help in directing the protein from the cytoplasm to a particular cellular compartments, that is from the nucleus to the endoplasmic reticulum, mitochondria, and other intracellular organelles. These specific peptides are recognized by receptors which are present on the membranes of particular organelles.

How Does Protein Trafficking Occur in Nucleus?

Nucleus is an important organelle in the cell, which controls all the cellular activities. It has a double layered membrane and contains genetic material, and presence of nucleus is a characteristic of eukaryotic cells. It contains a nuclear pore which allows specific proteins to move in and out of the nucleus. It controls the cell reproduction and its growth. Protein transporting in the nucleus is difficult because of its dual layer. The proteins found within the nucleus such as DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) polymerases, histones and transcription factors have a N-terminal signal sequence which is called a nuclear localization signal (NLS). This pathway includes nuclear pore complex and importin adapter proteins.

The mechanism in nucleus involves:

• The nuclear pore complex is a protein complex present in the nuclear envelope which connects the nucleoplasm and cytoplasm and is made up of 50 different proteins called nucleoporins or nups, which form an octagonal open pore. This complex helps in export and import of molecules from the nucleus.

• Antenna-like fibrils are present on the nuclear membrane facing towards the cytoplasm, which help in guiding the proteins to the nuclear pore.

• The protein that enters into the nuclear pore contains nuclear localization signals. The cytoplasm contains importin-α protein binds to the NLS and importin-β.

• Importin-β is recognized by nuclear pore and gets bound to it. During this transport, phenylalanine-glycine repeats which are present in the nucleoporin subunits.

• After the transportation of nucleoprotein-importin complex into the nucleus, its dissociation occurs with the help of ran-GTP and a small GTPase and the nucleoprotein is released into the nucleus.

How Does Protein Trafficking Occur in Mitochondria?

Mitochondria are double layered organelle present in the cytoplasm, which generates chemical energy needed for biochemical reaction of cells. The chemical energy is stored in an adenosine triphosphate molecule. It contains its own DNA which is inherited from the maternal side. They regulate the cell’s metabolic activity, promote cell multiplication and growth, and also play a role in C (cell death).

The steps included are:

• The transport proteins are present in the outer membrane of mitochondria linked with the inner membrane, which helps in moving matrix-bound proteins from the cytoplasm.

• The complexes that help in trafficking of proteins across the outer membrane are made up of translocator outer membrane (TOM).

• Some proteins which get embedded in the outer membrane are transported by sorting and assembly machinery (SAM) complex and translocator inner membrane (TIM) help in moving proteins across the inner membrane.

• A consensus signal sequence is present on mitochondrial proteins, which are bound by cytosolic chaperones ,which cause their transport.

How Does Protein Trafficking Occur in Endoplasmic Reticulum?

Endoplasmic reticulum is the largest organelle present in the cytoplasm. It is a major area where C occurs. It also helps in calcium storage, lipid and steroid synthesis, protein folding and carbohydrate metabolism.

The proteins which are transported into endoplasmic reticulum have N-terminal signal sequence and secondary internal signal sequences, also called as signal patches.

The steps included are:

• The signal sequence by signal recognition protein (a G-protein, which exchanges GDP (guanosine diphosphate) to GTP (guanosine triphosphate) while protein’s signal sequence binding) initiates the insertion process.

• The protein which is attached to the signal recognition protein reaches to the SRP (signal recognition particle) receptor which is present in the endoplasmic reticulum’s membrane. SRP receptors can be present alone or along with translocon (bipartite translocation channel). This receptor is a GTPase and when associated with translocon it exchanges GDP to GTP.

• The rough endoplasmic reticulum which has ribosomes, are attached to the endoplasmic reticulum cytoplasmic surface with the help of nascent polypeptide and SRP.

• Energy is released from both translocon and nascent polypeptide and the new protein is released through the translocon and it is synthesized.

• After entering the lumen of endoplasmic reticulum, which contains a recognition site for signal peptidase, an enzyme called hydrolytic enzyme present in the lumen of endoplasmic reticulum snips off the signal peptidase.

• The remaining protein is synthesized, which is pushed through translocon and is deposited in the lumen.

• The proteins which are embedded in the membrane are transferred with the help of transmembrane proteins which have internal signal sequences and according to their location, they can be start-transfer or stop-transfer sequence.

• A single-pass transmembrane protein insertion occurs, where a stop-transfer sequence can cause the protein to get stuck in the endoplasmic reticulum membrane, and pushing a portion of protein outside the organelle, where the C-terminus remains in the cytoplasm and N-terminus in the endoplasmic reticulum lumen.

• Insertion of double-pass transmembrane protein occurs, when the initial stop transfer sequence which is present on the membrane of endoplasmic reticulum. After the stop-transfer sequence, another signal patch can cause a start-transfer sequence which will transfer the remaining protein into the endoplasmic reticulum lumen. Therefore, both C-terminus and N-terminus are present in the lumen, with a cytoplasmic loop hanging outside in the cytoplasm.

Conclusion

Intracellular protein trafficking is a major part in cell biology, whereas extracellular proteins are trafficked with the help of endocytosis. The protein trafficking in the cell occurs due to signal peptides or signal sequences. These specific signal peptides are recognized by receptors which are present on the membranes of particular organelles.