Protein Trafficking

Protein trafficking is the transport and movement of proteins throughout the cell or from the
cell to the extracellular environment. The major cellular component or organelle involved in
protein trafficking is the Golgi apparatus. Proteins that have been translated by the
endoplasmic reticulum are first transported to the Golgi by a dedicated carrier called a
vesicle. The Golgi can modify the protein if needed. The Golgi apparatus is essentially a
dynamic network of intima that can form vesicles to transport proteins. It can be obtained by
fusion with a transport vesicle to obtain the protein it carries. In the Golgi, proteins are
modified and classified according to their final destination, then packaged in vesicles and
sent on the way. Protein trafficking is the transport of proteins to their correct subcellular
compartments or to the extracellular space (“secretory pathway”). Endo- and exocytosis
describe vesicle budding and fusion at the plasma membrane and are by most authors not
included in the term protein trafficking. Protein quality control comprize all cellular
mechanisms, monitoring protein folding and detecting aberrant forms.

Regulation of Protein Trafficking :

Protein trafficking is the transport of proteins to their correct subcellular compartments or to

the extracellular space (“secretory pathway”). Endo- and exocytosis describe vesicle
budding and fusion at the plasma membrane and are by most authors not included in the
term protein trafficking. Protein quality control comprize all cellular mechanisms,
monitoring protein folding and detecting aberrant forms.

Figure: Regulation of protein trafficking Protein

 Sorting and Transport:

Protein targeting or protein sorting is the biological mechanism by which proteins are
transported to their appropriate destinations within or outside the cell Proteins can be
targeted to the inner space of an organelle, different intracellular membranes, the plasma
membrane, or to the exterior of the cell via secretion. Information contained in the protein
itself directs this delivery processCorrect sorting is crucial for the cell; errors have been
linked to multiple disease-states.

In addition to the presence of a nucleus, eukaryotik cells are distinguished from prokaryotik
cells by the presence of membrane-enclosed organelles within their cytoplasm. These
organelles provide discrete compartments in which specific cellular activities take place, and
the resulting subdivision of the cytoplasm allows eukaryotic cells to function efficiently in
spite of their large size (about a thousand times the volume of bacteria).

Because of the complex internal organization of eukaryotik cells, the sorting and targeting of
proteins to their appropriate destinations are considerable tasks. The first step of protein sorting
takes place while translation is still in progress. Many proteins destined for the Endoplasmic
reticulum , the Golgi aparatus, lysosomes, the plasma membrane, and secretion from the cell
are synthesized on ribosones that are bound to the membrane of the endoplasmic reticulum. As
translation proceeds, the polypeptide chains are transported into the endoplasmic reticulum,
where protein folding and processing take place. From the endoplasmic reticulum, proteins are
transported in vesicles to the Golgi apparatus, where they are further processed and sorted for
transport to lysosomes, the plasma membrane, or secretion from the cell. The endoplasmic
reticulum, Golgi apparatus, and lysosomes are thus distinguished from other cytoplasmic
organelles by their common involvement in protein processing and connection by vesicular
transport.

Machanism of Protein Trafficking :

The secretory and endocytic pathways in eukaryotic cells serve as major routes for protein
transport out of and into the cell. Proteins enter the secretory pathway by translocation into
the endoplasmic reticulum. Subsequent protein transport between organelles of the
secretory pathway is mediated in large part by membranous carriers that bud from a donor
organelle membrane then dock and fuse with the appropriate recipient organelle. Similarly,
membrane-bounded carriers shuttle proteins through the endocytic pathway and also
between the secretory and endocytic pathways.
Steps of Protein Trafficking :

1. In the first stage of protein trafficking, translated proteins from the rough endoplasmic
reticulum are carried to the Golgi apparatus by vesicles.

2. Once the proteins reach the Golgi, they are modified by specific enzymes.
3. According to the cis-maturation model, proteins are carried through the appartus as the
cisternae they reside in migrates from the cis to the trans side of the Golgi stack.

4. Once they reach the trans Golgi network (TGN), proteins are again packaged into
vesicles and distributed elsewhere to their final destination.
5. According to the cis-maturation model, proteins are transported through the Golgi stack
because the pool containing them migrates or matures in the cis-trans direction. As the
trans Golgi network
vesicles mature, new vesicles from the ER continue to provide new cis libraries.

6. Within the trans Golgi network, proteins are sorted by their final destinations. This is
accomplished by receptor molecules embeddedin the membrane of the TGN.
7. When proteins have reached their correct location within the TGN, the membrane at
those locations buds off into vesicles. More than one protein can be contained within
each transport vesicle.

8. 8.Once released, the vesicles carry their cargo proteins to a final location. Possible
destinations include the lysosome, the digestive organelle of the cell, and the plasma
membrane, where the proteins can be released elsewhere in the organism.
Regulation of nuronal function by protein trafficking :

Protein trafficking plays a central role in many aspects of neuronal function, from the release
of neurotransmitters by exocytosis and the recycling of synaptic vesicle proteins to the
regulation of receptor signalling. Synaptic function can be significantly modified on a short
time scale by alterations in the levels of receptors, ion channels and transporters both pre- and
postsynaptically. In many cases, these alterations appear to be mediated by acute changes in
the rates at which the proteins are endocytosed from and exocytosed to the cell surface from
intracellular pools. While our current understanding of the signalling mechanisms and the
intracellular pathways responsible for these acute changes is still in its infancy, intriguing
details are beginning to emerge from a number of systems.

Interest in regulatory mechanisms controlling the activity of synaptic proteins has directed
renewed attention to protein trafficking as a potential mediator of synaptic plasticity. A major
goal in neuroscience has been the elucidation of the molecular mechanisms that underlie the
ability of higher organisms to learn and remember. At a cellular level, these processes are
thought to be mediated by both long- and short-term changes in the signalling properties of
neurons. Due to remarkable advances in molecular biology in the past 10 years,
neuroscientists can now envision that such changes in synaptic function can be achieved by
altering levels of key proteins involved in synaptic transmission, including synaptic vesicle
proteins, neurotransmitter receptors and neurotransmitter transporters. While long-term
changes in protein expression are frequently the result of alterations in mRNA levels and
increased protein synthesis, acute changes in protein distribution may involve regulation of
protein trafficking, in particular in the endosomal pathway.