3 minute read
Receptors
other cells what identity they need to take on. It also happens in synaptic signaling between two nerve cells. As mentioned in the previous chapter, neurotransmitters cross the gap between cells to send signals between the cells. The neurotransmitter is either degraded or taken back up into the sending cell so another signal can be sent.
Autocrine signaling involves a cell signaling itself, releasing a ligand that binds to its own receptors. It is important during development as cells take on their identity. It is important in cancer and in cancer metastases. Signals can be both autocrine and paracrine at the same time.
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Endocrine signaling happens over the longest distances. It makes use of the circulatory system in order to pass a signal from one place to another. The signal goes through the bloodstream in order to get from one place to another in the organism. The target cell can be anywhere in the organism’s body. The cell signals in such cases are referred to as hormones.
Signaling can happen through direct cell to cell contact. This happens through connections called plasmodesmata (in plants) and gap junctions (in animals). These allow for intracellular mediators to diffuse between the cells so both cells have the same signal. This especially connects things like ions but will not allow larger molecules to pass between the cells. Plasmodesmata connect practically every plant cell together in the organism.
When cell signaling happens, it starts with a ligand and a receptor. A receptor can match just a single or a few ligands to it in a sort of lock-and-key mechanism. When the ligand binds the receptor, it changes the shape or activity of the receptor so that there is an intracellular change.
RECEPTORS
There are two types of receptors. There can be intracellular receptors inside the cell (nucleus or cytoplasm) and cell surface receptors (on the plasma membrane). Most intracellular receptors are small hydrophobic molecules that can cross the plasma membrane. These include the different steroid hormones, like sex hormones. These intracellular receptors often induce a change in gene activity, regulating transcription.
Cell surface receptors are membrane-bound proteins that bind to specific ligands outside of the cell. The ligand never has to cross the plasma membrane so they can be large, hydrophilic molecules. The cell surface receptor has three different domains. There is an extracellular, ligand-binding domain, a hydrophobic domain (inside the plasma membrane), and an intracellular domain. The hydrophobic part can go in and out of the membrane several times.
Ligand-gated ion channels involve ion channels that can open up after binding a ligand. There is a hydrophobic part that is in the membrane with a hydrophilic core. After binding the ligand, the core opens up so that the ions can pass through the membrane opening. In most cases, the ligand binding will open a channel but in other cases, the ligand binding will close the channel. Neurons have ligand-gated channels that connect to neurotransmitters. Figure 51 shows a ligand-gated ion channel in action:
Figure 51.
G protein-coupled receptors or GPCRs will be discussed in a minute. These are actually a family of cell surface receptors that traverse the membrane seven different times. They transmit signals inside the cell through a G-protein. Many different ligands will bind to these types of receptors. The smell receptors are G protein-coupled receptors.
All G proteins will bind to GTP, which breaks down to make GDP. A G protein attached to a GTP molecule is considered “on”, while a G protein that’s bound to a GDP molecule is considered “off”. The G proteins have three subunits called heterotrimeric G proteins.
There are enzyme-linked receptors that are cell-surface receptors linked to an enzyme. In some cases, there is a part of the receptor that is actually an enzyme. Others will just interact with an enzyme. Receptor tyrosine kinases are types of enzyme-linked receptors. As you’ll remember, kinases are enzymes that phosphorylate other substances. In this case, tyrosine kinase transfers phosphate groups to tyrosine.
Two nearby receptor tyrosine kinases will come together or “dimerize”. The receptors then are able to attach phosphates to each other’s domains. The phosphorylated tyrosine molecules are able to transmit a signal to other molecules within the cell. It takes two receptor tyrosine kinase molecules together in order to cause the phosphorylation of tyrosine.
These receptor tyrosine kinases are important to signaling processes. They bind to growth factors that help to promote cell survival and cell division. There are different growth factors, such as nerve growth factor and platelet-derived growth factor, which are related to the tyrosine kinase receptors. Certain cancers are related to overactivity of these receptors. Figure 52 shows the tyrosine kinase activity with respect to these receptors: