User:Ecodj001/Intracellular transport

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Lead

Intracellular transport generally refers to the movement of substances within vesicles of a cell. By responding to physiological signals, intracellular transport is needed by the cell for ensuring homeostasis. The cytosol contains synthesized proteins; these get distributed to their respective organelles, based on the sequence of their specific amino acid’s sorting. Eukaryotic cells transport packets of components to particular intracellular locations by attaching them to molecular motors that haul them along microtubules and actin filaments. Intracellular transport greatly depends on microtubules for movement. Considering this, it can be inferred that the components of the cytoskeleton are very essential towards the trafficking of vesicles between organelles and the plasma membrane by providing mechanical support. This pathway makes it possible for the cell to facilitate the movement of essential substances such as membrane‐bounded vesicles and organelles, chromosomes, and mRNA.

General representation of intracellular protein transport

One thing that makes the intracellular transport in eukaryotic cells unique is that eukaryotic cells are made up of organelles enclosed in membranes that need to be mediated for exchange of cargo to take place. On the other hand, prokaryotic cells do not possess membrane-bound organelles and compartments to traffic between. Hence, this specialized transport mechanism does not occur in prokaryotes. Prokaryotes are able to function and survive through the process of simple diffusion. The general idea suggest that intracellular transport is more specialized than simple diffusion; it comprise of a diverse array of processes which make use of transport vesicles. Transport vesicles are useful for holding cargo; they are very small structures found within the cell and consist of fluids enclosed by a lipid bilayer. They function by typically initiating processes such as cargo loading, vesicle budding, vesicle transport, and binding and fusion of the vesicle to a target membrane. In order for the vesicles to embark in the right direction and to ensure an appropriate organization of the cell, special motor proteins attach themselves to cargo-filled vesicles and carry them along the cytoskeleton. For instance: transferring lysosomal enzymes to another part of the cell, other than the Golgi apparatus, could result in a deleterious effect. Hence, they would have to ensure that the lysosomal enzymes are transferred specifically to the Golgi apparatus.

Fusion

In endocytic and secretory pathways, it is very common to find small membrane-bound vesicles that transport proteins from one organelle to another. These vesicles first bud from their donor organelle and then fuse with their target organelle. After the fusion, they then release their content into the target organelle. For proteins to reach their final destination, they would have to pass through the Endoplasmic reticulum, which serves as a channel. For the outbound proteins to reach their final destinations, they bud from the endoplasmic reticulum and travel along the cell cortex. The ER also serves as the site for protein synthesis, as well as the parent organelle for proteins. The transported protein signals are received through the cis face of the Golgi, which is typically termed as the acceptor.

A class of proteins, termed as Rab proteins, are located on the surface of the transport vesicles. For a fusion event to occur, these proteins ensure a proper alignment with the complementary tethering proteins found on the cytosolic surface of the respective organelle. After the fusion event, delivery of the vesicle's contents occurs, and this process is mediated by SNARE proteins among others. SNARE proteins are small proteins with anchored tails that function by inserting their tails into membranes, hence supporting the fusion event and initiating the transport between vesicles and organelles in the cytosol. The two forms of SNARES are the t-SNARE and the v-SNARE. The t-SNAREs function by binding to the membranes of the target organelles, while the v-SNAREs function by binding to the vesicle membranes.

How SNAREs partake in fusion

Role of endocytosis

Through the process of intracellular transport, cells obtain nutrients and signals. And this process can be categorized into different forms. One of these forms of intracellular transport is the process of endocytosis. Endocytosis refers to the engulfing of materials into a cell. Atypical example of endocytosis in eukaryotic cells is phagocytosis. This refers to the ingestion of bacteria or other material into a cell to form a phagosome. Phagocytosis is very important in the process of intracellular transport -- once a substance is detected as harmful and engulfed in a vesicle, it can be channeled to the appropriate location for it to be degraded. This potential is very necessary for the destruction of any foreign material that is toxic or unuseful for the cell; In this way, phagocytosis, which is a form of endocytosis, play an important role in the immunologic and apoptotic function of the cell.

Role of microtubules

A cytoplasmic dynein motor bound to a microtubule. A kinesin molecule bound to a microtubule.

How microtubules play a role in intracellular transport

The general idea of the transport mechanism is to initiate the movement of materials. Intracellular transports that require quick movements usually make use of an actin-myosin mechanism. On the other hand, more specialized functions make use of microtubules for transport. Microtubules give structure to the cell to help it resist compression and also provide a highway in which vesicles move across the cell in the process of transporting materials. This process is powered by motor proteins such as dynein. The motor proteins function by connecting the transport vesicles to microtubules and actin filaments, in order to facilitate intracellular movement. The organization of microtubules is such that their plus ends extend through the periphery of the cells, while their minus ends are anchored within the centrosome. This orientation suggests that they make use of the motor proteins kinesins and dynein to transport vesicles and organelles in opposite directions through the cytoplasm. The kinesins are the positive directed ends, and the dynein are the negative directed ends. A very important function of microtubules is to transport membrane vesicles and organelles through the cytoplasm of eukaryotic cells.

Diseases

Now that the general mechanisms of intracellular transport have been understood, it is easier to see how it plays a role in diseases. Several factors occur that can lead to the occurrence of diseases when it comes to intracellular transport. Typical examples of these factors include improper sorting of cargo into transport carriers, improper movement of vesicles along cytoskeletal tracks, and defective fusion at the target membranes. The life cycle and intracellular transport in cells is a highly regulated and vital process. Hence, if any of the processes in the series goes wrong, there is a higher possibility for the occurrence of deleterious effects. When this happens, it will likely lead to the formation of protein aggregate, which will further lead to the formation of diseases. Several evidence has supported the stance that the occurrence of deficits in axonal transport leads to pathogenesis in several neurodegenerative diseases. One important fact is that protein aggregation caused by faulty transports is a leading cause of neurodegenerative diseases such as ALS, Alzheimer’s and dementia.

As a way of counteracting these defects, the intracellular transport processes of these motor proteins can be targeted. This procedure constitutes the possibility for pharmacological targeting of drugs. Having gain knowledge on how substances move along neurons or microtubules, this provides clarity on how to target specific pathways in an attempt to battle diseases. As an importance of this study, pharmaceutical companies are making use of intracellular transport as a means of targeting certain components of the cell as a way of fighting certain diseases such as cancer and others.