Introduction to Cellular Communication *

Transcription

1 OpenStax-CNX module: m Introduction to Cellular Communication * Steven Telleen This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution License Why Cells Communicate Both internal and external cellular communication are essential for living organisms. Internally cells need to communicate between the various biochemical steps and processes carried out within the cell. Externally cells need to communicate with other cells to coordinate activities, whether they are bacterial colonies or dierentiated cells coordinating infrastructure activities within the organism. Recent studies also have demonstrated important communication taking place between bacterial cells (often in the GI tract) and cells in other areas of their host organism. All of these forms of cellular communication use similar mechanisms. It is worth keeping in mind that communication refers to the Signal -> Target -> Response activities at the chemical level and does not imply any sort of conscious activity or understanding on the part of the participating cells or proteins. At the highest level there are two kinds of communication in the world of living cells. Communication between cells is called intercellular signaling, and communication within a cell is called intracellular signaling. An easy way to remember the distinction is by understanding the Latin origin of the prexes: intermeans "between" (for example, intersecting lines are those that cross each other) and intra- means "inside" (like intravenous). Often the intracellular communication processes initially are triggered by extracellular signals. Biological communication has several steps. In intercellular communication the target cell must convert the external signal into an internal response in order for the communication to be successful. The originator of the communication generates a message called a signal. The signal must be received by the target. The target cell then transduces the signal into a response. (Figure 1) * Version 1.1: Mar 14, :29 pm

2 OpenStax-CNX module: m Figure 1: Communication between two cells involves three stages: Reception of the signal from the initiating cell, Transduction of the signal via intracellular pathways, and a Response (change) in the receiving cell. The initial cellular response generally involves opening a channel or activating either an internal enzyme or a high-energy chemical molecule. Generating the response often requires additional internal communication, where the rst response becomes a signal for an internal target protein that responds by creating one or more additional signals for other proteins. This intracellular communication process continues until the nal cellular response is achieved. This is an example of the generic cause-and-eect-chain process discussed in the rst chapter, An Introduction to the Human Body. In this context the cause and eect chain is called a transduction pathway. Chemical signals are released by signaling cells in the form of small, usually volatile or soluble molecules called ligands. A ligand is a molecule that binds with another specic molecule, in some cases, delivering a signal in the process. Ligands can thus be thought of as signaling molecules. Ligands interact with proteins, called receptors, in target cells, which are cells that are aected by the chemical signal. Ligands and receptors exist in several varieties; however, a specic ligand will have a specic receptor that typically binds only with that ligand or chemicals similar to that ligand (for example agonists and antagonists). You may want to review the section on enzymes in the Cellular Metabolism chapter as the ligand/receptor part of the process works in a similar way in both activities.

3 OpenStax-CNX module: m Intercellular Communication Mechanisms There are two fundamentally dierent forms of communication between cells, direct and indirect. Direct communication occurs between cells that are physically connected. The signals pass from one cell to another through cytoplasmic uid. Indirect communication involves chemical diusion across the interstitial uid between cells. (Figure 2) Direct communication in animal cells takes place through gap junctions. These water-lled channels between the cells allow small signaling molecules, called intracellular mediators, to diuse between the two cells. Small molecules, such as calcium ions (Ca 2+ ), are able to move between cells, but large molecules like proteins and DNA cannot t through the channels. The specicity of the channels ensures that the cells remain independent but can quickly and easily transmit signals. The transfer of signaling molecules communicates the current state of the cell that is directly next to the target cell; this allows a group of cells to coordinate their response to a signal that only one of them may have received. In plants, the equivalent of gap junctions (plasmodesmata) are ubiquitous, making the entire plant into a giant, communication network. Indirect communication always involves the release of the signal into interstitial uid outside the signaling cell and diusion of the signal molecules to surrounding cells. With one major exception the target cells are within diusion distance of the signaling cell. The exception is found in signal molecules that are released into an area of dense capillary beds. In this case the signal molecules diuse from the interstitial uid into the blood stream where they are distributed into the interstitial uid throughout the body.

4 OpenStax-CNX module: m Figure 2: Cell signaling can be organized into a hierarchy of categories: Direct vs. Indirect > Indirect = Paracrine vs. Hormonal > Paracrine = General vs. Autocrine vs. Neuronal. Hormonal Signaling Hormones are ligands that reach their targets by traveling in the blood. As such, they are signaling molecules that are produced in one part of the body but aect cells in other body regions some distance away. In the body, many hormones originate from endocrine cells. Endocrine cells are located in endocrine glands, such as the thyroid gland, the hypothalamus, and the pituitary gland. However, cells in non-endocrine organs, such as the heart, kidney, and adipose tissue, also release hormones into the blood. Hormones travel long distances between the signaling cells that released them and their target cells via the bloodstream, which is a relatively slow way to move throughout the body. While these blood-borne signals usually produce a slower response they also have a longer-lasting eect. The same hormone also can aect multiple organs with one release. Because of their form of transport, hormones get diluted and are present in low concentrations when they act on their target cells. This is dierent from paracrine signaling, in which local concentrations of ligands can be very high.

5 OpenStax-CNX module: m Paracrine Signaling Signals that act locally between cells that are close together are called paracrine signals. Paracrine signals move by diusion through the extracellular matrix. Although paracrines may enter the bloodstream, their concentration is generally too low to elicit a response from distant tissues. A familiar paracrine example experienced by those with allergies is histamine, a paracrine released by immune cells (basophils and mast cells). Histamines increase the permeability of the capillaries to white blood cells and some proteins allowing them to engage pathogens in infected tissues. When the immune system mistakenly targets non-pathogenic material the histamine release causes the symptoms (excess uid, runny nose, and watery eyes) seen in allergies. Antihistamines are taken to counter the eects of this paracrine. Paracrine communication also is critical for cell dierentiation during development. The paracrine signals released by surrounding cells determine the specic dierentiation pathway of developing stem cells. These same paracrines either released by mature cells in the area of placement or articially introduced guide the correct dierentiation and development of embryonic stem cells in stem cell therapies. In addition to general paracrine communication with the local cells there are two special types of paracrine action: autocrine and neuronal. Autocrine communication occurs when the cell releasing the paracrine also has receptors for and responds to the paracrine it is releasing. This is a form of self communication, but instead of communicating using intracellular pathways the cell "talks to itself" via extracellular mechanisms. The prex auto- means self, a reminder that the signaling cell sends a signal to itself. This type of signaling often occurs during the early development of an organism to ensure that cells develop into the correct tissues and take on the proper function. In some cases, neighboring cells of the same type are also inuenced by the released ligand. In embryological development, this process of stimulating a group of neighboring cells may help to direct the dierentiation of identical cells into the same cell type, thus ensuring the proper developmental outcome. In the immune response autocrine signals, called interleukins, create a positive feedback loop in T-Helper cells rapidly amplifying the response. Autocrine signaling also regulates pain sensation and inammatory responses. Further, if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process. Neuronal communication allows the signaling cells (neurons) to release the chemical ligands, called neurotransmitters, a long distance from the cell body. Physical extension of the cell itself (the axon) spans the long distance to a specic target so the ligand is released in a space very close to the target cell called a synapse. The ability to communicate with distant targets is a trait shared with hormonal communication. However, unlike the widespread distribution of hormonal ligands the release of the neurotransmitter happens very close to the target cell and only aects a small area near the target. This makes the concentration of neurotransmitter near the target receptors much higher than the concentration of ligand around hormonal target receptors. The ligand itself only diuses a short distance to the target and is rapidly broken down or removed from the area of release, making it a form of paracrine communication. note: A nerve cell consists of a cell body, several short, branched extensions called dendrites that receive stimuli, and a long extension called an axon, which transmits signals to other nerve cells or muscle cells. The junction between nerve cells where signal transmission occurs is called a synapse. Signals within the nerve cells are propagated down the axon by fast-moving electrical impulses. When these impulses reach the end of the presynaptic cell's axon, the signal is communicated to the postsynaptic cell by the release of chemical ligands called neurotransmitters. The neurotransmitters diuse across the very small distances between nerve cells (synapses) (Figure 3). The small distance between nerve cells allows the signal to diuse quickly; this enables an immediate response, such as, Take your hand o the stove!

6 OpenStax-CNX module: m Figure 3: The distance between the presynaptic cell and the postsynaptic cellcalled the synaptic gapis very small and allows for rapid diusion of the neurotransmitter. Enzymes in the synapatic cleft degrade some types of neurotransmitters to terminate the signal.

7 OpenStax-CNX module: m When the neurotransmitter binds the receptor on the surface of the postsynaptic cell, the electrochemical potential of the target cell changes, and the next electrical impulse is launched. The neurotransmitters that are released into the chemical synapse are degraded quickly or get reabsorbed by the presynaptic cell so that the recipient nerve cell can recover quickly and be prepared to respond rapidly to the next synaptic signal. 3 Summary Cells need to communicate to coordinate activities taking place both inside their own cytoplasm and with other cells. The former is called intracellular communication and the later extracellular communication. Intracellular communication often is triggered by an extracellular signal and is used to generate the response. The internal communication chain that connects the external signal to the internal response is called a transduction pathway, and the process can be summarized as the three stage process: Signal -> Transduction -> Response. Communication between cells can be either direct, where their cytoplasm is connected by gap junctions, or indirect, where the signal is released into the extracellular uid around the signaling cell. Indirect communication has four components: a signaling cell, a signal molecule (called a ligand), and a target cell, that has a receptor protein that responds to the ligand. Indirect communication can be dierentiated by the proximity of the signal release to the target. Paracrine communication occurs when the signaling cell releases the signal molecule (called a paracrine) close to the target and the molecules reach the target receptors solely by diusion through the interstitial uid. Hormonal communication occurs when the signal molecule (called a hormone) diuses into the blood stream and is distributed to interstitial uid all around the body. Hormonal communication can target cells that are a great distance from the signalling cells and a given signal can aect many dierent types of cells simultaneously. In addition to general paracrine communication, there are two special types of paracrine activity. Autocrine communication is used to describe signaling cells that have receptors for their own signaling molecules. They are both the signal initiator and the target cell. Neuronal communication refers to the special case of neurons. Like hormonal communication, neuronal communication can span long distances. Unlike hormonal communication: 1) the distance is spanned by physically extending a portion of the neuron itself (the axon) to the target cell, 2) the signal molecule (called a neurotransmitter) only diuses through the interstitial uid in the synapse, and 3) the target cell is very specic, even more specic than general paracrine targets. 4 Review Questions Exercise 1 (Solution on p. 9.) The secretion of hormones by the pituitary gland is an example of. a. autocrine signaling b. paracrine signaling c. endocrine signaling d. direct signaling across gap junctions Exercise 2 (Solution on p. 9.) Endocrine signals are transmitted more slowly than paracrine signals because. a. the ligands are transported through the bloodstream and travel greater distances b. the target and signaling cells are close together c. the ligands are degraded rapidly d. the ligands don't bind to carrier proteins during transport

8 OpenStax-CNX module: m Free Response Exercise 3 (Solution on p. 9.) What is the dierence between intracellular signaling and intercellular signaling? Exercise 4 (Solution on p. 9.) How are the eects of paracrine signaling limited to an area near the signaling cells?

9 OpenStax-CNX module: m Solutions to Exercises in this Module to Exercise (p. 7) C to Exercise (p. 7) A to Exercise (p. 8) Intracellular signaling occurs within a cell, and intercellular signaling occurs between cells. to Exercise (p. 8) The secreted ligands are quickly removed by degradation or reabsorption into the cell so that they cannot travel far.