Archives for category: receptor

3- Transport by vesicles: when proteins are made on the rough endoplasmic reticulum (RER), they get loaded into the Golgi apparatus. They are then sorted, modified and packaged in vesicles made from the budding-off of the Golgi membrane and discharged.

Sorting signals directs the protein to the organelle. The signal is usually a stretch of amino acid sequence of about 15-60 amino acids long.

There are at least three principles that characterize all vesicles mediated transport within cells:

                      i.        The formation of membrane vesicles from a larger membrane occurs through the assistance of a protein coat such as clathrin that engulfs the protein because an adapter protein such as adaptin binds both to the coat and to the cargo protein bringing both close together.

Clathrin-coated vesicle transport. Click on image for credit.

The adaptin traps the cargo protein by biding with it’s receptors. After assembly particles bind to the clathrin protein they assemble into a basket-like network on the cytosolic surface of the membrane to shape it into a vesicle. Their final budding-off requires a GTP-binding protein called dynamin.

                    ii.        The process is facilitated by a number of GTP-binding proteins (ex; dynamin) that assemble a ring around the neck of a vesicle and through the hydrolysis of the phosphate group of GTP to GDP until the vesicle pinches off. In other words, GTP is one of the main sources of cellular energy for vesicle movement and fusion.

Dynamin powered by GTP pinches the vesicle off the membrane. Click on image for credit.


Another picture of the same process. Click on image for credit.

                   iii.        After a transport vesicle buds-off from the membrane, it is actively transported by motor proteins that move along cytoskeleton fibers to its destination. The vesicle then fuses with a target membrane and unloads the cargo (protein). But in order to fuse a vesicle with the membrane of another compartment, they both require complementary proteins, which in this case is soluble N-ethylmalei mide-sensitive-factor attachment protein receptor or, ahem, SNARE present in the membrane – one for the vesicle (vesicular SNARE) and one for the target membrane (t-SNARE).

SNARE helping direct transport vesicles to their target molecules. Click on image for credit.

Each organelle and each type of transport vesicle is believed to carry a unique SNARE. Interactions between complementary SNAREs helps ensure that transport vesicles fuse only with the correct membrane.

Membrane fusing does not always follow immediately after docking (unloading of cargo), however it often waits for specific molecular signals.

Btw, based on coat protein, transport proteins can be classified into three types:


Coated Vesicle Types.

COP stands for Coatamer proteins (COP) which is the second class of coat protein that mediates budding-off of vesicles from large membranes. It can be of two types I (anterograde; moving in a forward direction. Ex; from ER to Golgi) & II (retrograde; moving in a backward direction. Ex: from Golgi back to ER).

2-  Transport across membranes: Similar to how transport functions via the nucleus, most proteins are transported across the biomembrane with the help of receptor proteins which form a complex with the import molecule.

Protein translocators located between the biomembrane (transmembrane protein or integrins) identifies the signal sequence by unfolding the protein and transports it across the membrane into the organelle or cell (similar to the way NPCs do).

Once the protein enters the organelle or cell, its signal sequence is cut off by a peptidase enzyme and the protein is folded into its final 3-D shape again with the help of helper molecules.


In the case of proteins intended for secretion out of the cell, as soon as their N-terminal contains the signal sequence that will indicate this, a signal recognition particle binds to it and forms a protein complex causing synthesis to slow down. The SRP-protein complex will travel and bind to a SRP-receptor on a rough endoplasmic reticulum (RER) membrane. Once the protein gets to the RER membrane, its synthesis will continue at the normal rate until it is complete. During translocation out of the cell, the signal sequence is cut off by a signal peptidase located in the RER membrane and released from the translocation channel and degraded to amino acids.

RER serves as an entering point for proteins that have to go to other organelles like the Golgi complex and lysosome. They can also ferry proteins out of the cell by transport vesicles formed from the budding off of their biomembrane.


There are three mechanisms in which newly synthesized proteins are inserted into the RER membrane (the mechanisms vary with the type of protein);

  • Type I; signal sequence on N-terminals enters first and continues to elongate until a hydrophobic stop-sequence is reached, and then inserted in the membrane and forms the anchor for that protein. Of course then signal sequence is cut by protease.
  • Type II; these proteins have rather long hydrophobic regions that will be anchored in the membrane with the C-terminal leading. Protein continues to be inserted until it reaches the hydrophobic stop-sequence, but the signal sequence is not cut.
  • Type III; same as type I, the only difference is that the signal sequence is not cut.


And according to the number of times that protein passes through the membrane, the proteins of the ER membrane can be divided into single pass transmembrane protein, double pass transmembrane protein, and multi-pass transmembrane protein.


I understand the information here may appear bland. This is because it has been generalized for most process within the cell and cell biologists study the various pathways that exist which can be very overwhelming. Here a brief overview is being discussed such that when you choose to do more detailed study, this generic pattern would have provided you with a basic background.

When protein sorting occurs, they are imported into different places via one of the following three ways:

1-    Transport through nuclear pores: Nuclear pores are large complex structures in the nuclear envelope (double-membrane) that regulate movement of macromolecules (proteins and nucleic acids) in and out of the nucleus.

The nuclear envelope has many nuclear pores termed nuclear pore complex (NPC).

Nuclear Pore Complex

In the nucleoplasmic face of the NPC, a nuclear ring supports eight basket filaments joined by the terminal ring forming a structure called the nuclear basket. In the cytoplasmic face, the NPC’s cytoplasmic ring supports eight cytoplasmic filaments. In the center of the NPC, there are the central plug or transporter (protein) and spoke which connect the two ring subunits together.

Nuclear Pore Complex2. Click on image for credit.

This complex provides the nucleus with the ability to selectively allow entry and exit of molecules. Ions, metabolites, and small proteins can pass freely and nonselectively between the nucleus and the cytosol.

Large molecules, however, and macromolecular complexes carry sorting signals called nuclear localization signals (NLS) to which a nuclear import receptor protein (NIRP) will bind and direct through the pore. The NIRP are also called nuclear transport receptors (NTR) and leads the proteins (synthesized in the cytoplasm but required for the nucleus) into the NPC,

The transport process via NPCs.

The NIR attaches to the NLS of the protein that wants to enter the nucleus, forming a NIR-protein complex, and delivers it in through the NPC.

Once inside, one of the proteins of the NPC is an enzyme named Ran-GTPase which functions to add the protein complex Ran-GTP to the NIR-protein complex and causes conformational changes in the latter’s polypeptide chain leading to the dissociation of the NIR from the protein intended for the nucleus. Ran-GTP is a complex of Ran protein attached to guanosine triphosphate (a nucleoside).

The NIR-Ran-GTP complex formed, then, is powered by GTP hydrolysis to GDP (guanosine diphosphate– di meaning two, as in only two phosphate groups remain attached to the guanosine nucleoside molecule) and exit the nucleus through the NPC. The Ran-GTP is thus converted to Ran-GDP which, once the NIR-Ran-GDP complex exits the nucleus, will dissociate from the NIR.

Nuclear export works similar to nuclear import, but in reverse and proteins contain a nuclear-export signal (NES).

Two important concepts will be discussed in this chapter. One is that of the membrane-enclosed organelles which are thought to have evolved in at least two ways:

  1. The nuclear membrane and the membrane of the endoplasmic reticulum, Golgi apparatus, endosomes, and lysosomes are believed to have originated by invagination (inner folding) of the plasma membrane. These membranes and the organelles they enclose (except for the nucleus) are all part of the endomembrane system.

    Simplified illustration of invagination.

  2. Mitochondria and chloroplasts are unique because they have their own DNA that loops in a circle like that of bacteria. And they manufacture many of their own proteins and reproduce by binary fission so they may have evolved in the sense that they were prokaryotes (primordial single-cells) that became so dependent on their host that they are now a part of the cell.


The other important concept is the fact that a typical mammalian cell contains about 10,000 different kinds of proteins. For a cell to work properly, each of these many proteins must be sent to the correct place. The process of directing each newly made polypeptide to particular destination is known as protein targeting or protein sorting.

The proper organelle destination for a protein is determined by signals in the amino acid sequence that will ultimately bind to a receptor protein involved in importing that protein into the organelle.

In some cases, there is a single sequence at the N-terminal which are called signal sequences or signal peptide. And in other cases there are one or more internal sequences that are not in a continuous series called signal patch. Because this sequence is composed of two separate elements, it is referred to as bipartite (being or having two-bi parts-partite).

Different types of signal sequences.

Signal patch are formed because when the protein is made, it is folded and since a fold can bring different regions together (think of smudged paper that can bring the corners of the paper close to the center), the juxtaposition of amino acids from far regions that are physically separated before the protein folds will contain the signal in series (now imagine colouring the smudged paper. After unfolding it, the paper will appear to be coloured in patches). Btw, protein can be synthesized inside the cell or come from outside, and in those two cases it will still have a sequence.

All for now.