Conceptual Assessment of Physiology

Cell-Cell Communications

This Cell-Cell Communications concept is summarized as: the function of the organism requires that cells pass information to one another to coordinate their activities.

The following version of the Cell-Cell Communications Conceptual Framework CC-CF was sent out in a survey to physiology faculty (Michael et al, A Conceptual Framework for the Core Concept of Cell-Cell Communications. FASEB J 2016, 553.20, paper under review.) The CC-CF contains 51 items organized into four hierarchical levels starting with critical components. The CC-CF has been formatted in a way to make clear the hierarchical organization. It describes its domain in a way that should be useful for teaching and learning in introductory courses through medical students. However, we recognize that lower-division undergraduate physiology courses may focus on different underlying constituent ideas than upper-division or professional school courses.

CC1. A cell synthesizes and releases a chemical messenger.

CC1.1 A cell synthesizes a messenger molecule.

CC1.2 Messenger molecules can be proteins (or peptides), steroids, or amines.

CC1.3 The rate of release of a messenger from a cell is determined by the “sum” of the stimuli for release and the stimuli that inhibit release.

CC1.4 Chemical messengers are present at very low concentrations in the blood compared to other biologically active molecules such as ions and nutrients.

CC1.5 The greater the net stimulus for release the higher the rate of release of the messenger.

CC1.6 Cells release messengers by exocytosis or diffusion across the cell membrane.

CC1.7 Cells that release messengers can be anywhere in the body.

CC2. Transport of messenger molecules is determined by the chemical nature of the messenger.

CC2.1 The solubility of the molecule determines how it is transported to its target cells.

CC2.1.1 Protein/peptide and amine messengers are generally water soluble and are transported in solution.

CC2.1.2 Steroid messengers are lipid soluble and are transported bound to protein carrier molecules in the blood.

CC2.1.3 Some amine messengers are transported bound to transport proteins and others are carried in solution.

CC2.2 The extracellular fluid concentration of a messenger molecule depends on the balance between production/release and elimination of the messenger.

CC2.3 Only the messenger in solution and free to diffuse is biologically active.

CC3. The messenger must bind to a receptor protein in or on its target cell to produce a response.

CC3.1 Each messenger molecule can only bind to a specific receptor molecule.

CC3.2 A cell can only respond to a messenger for which it has receptors.

CC3.3 The solubility of the messenger determines the location of its receptor protein in/on the target cell.

CC3.3.1 Water soluble messengers have receptors that on the target cell membrane.

CC3.3.2 Lipid soluble messenger have receptors that are inside the target cell, usually in the nucleus but in some cases in the cytoplasm as well.

CC3.4 The number of receptors for a particular messenger can be relatively small or relative large, and is variable.

CC3.5 There can be more than one type of receptor for the same messenger on different target cells.

CC3.6 Thus the same messenger can produce different responses in the same type of target cells wherever they may be in the body.

CC3.7 Cells have a large variety of different receptors, thus enabling them to respond to a large number of different messengers.

CC4. Binding of the messenger molecule to its receptor gives rise to signal transduction.

CC4.1 A single messenger molecule bound to its receptor can activate or alter many more molecules in the target cell; this is called amplification.

CC4.1.1 Because target cell response is a multi-step process, and amplification occurs at each step, a single molecule can activate or alter many more molecules; the more steps in the intracellular signaling process the greater the amplification can be.

CC4.1.2 Given that messenger molecules are scarce, if the signal is not amplified it will have little physiological effect.

CC4.1.3 Because the target cell response is a multi-step process there are many points at which different inputs (other messengers) can modify the outcome/response. This is referred to as integration.

CC4.2 Because the target cell response is a multi-step process, a particular messenger molecule can have more than one effect in a target cell.

CC4.3 There are two basic mechanisms for transduction, both of which result in amplification.

CC4.3.1 Binding of a messenger molecule to its receptor can activate a cascade of intracellular second messengers which result in altered enzyme activity.

CC4.3.2 Binding of a messenger molecule to its receptor can alter the processes of translation and transcription in the cell nucleus, thus altering the concentration of a specific enzyme in the cell.

CC4.3.3 The speed of the response of the two systems is different.

CC4.3.3.1 The speed of response in a second- messenger system is fast since second messenger molecules are already present in the cell.

CC4.3.3.2 The speed of response in transcription and translation systems is slower because new molecules have to be synthesized.

CC4.3.4 Persistence of the response to messenger molecules also differ.

CC4.3.4.1 In second messenger systems, the half-life of the molecules that get activated is short, and the response can be terminated quickly.

CC4.3.4.2 In translation/transcription-based systems, the half-life of the molecule (proteins) produced is longer, so the responses persist longer.

CC5. Binding of the messenger molecule to its receptor alters cell function.

CC5.1 The response of the target cell is a function of the target cell and not the messenger molecule. That is to say, the response to a given messenger is determined by the physiology of the target cell.

CC5.2 Alteration of target cell function is always the result of altering enzyme activity, whether caused by second messenger alteration of enzyme activity or by changes in translation/transcription causing the appearance of more enzyme molecules.

CC6. Termination of a messenger signal is accomplished in several ways.

CC6.1 The messenger signal goes away because the messenger molecule is no longer released or it is broken down.

CC6.2 The messenger molecule is removed from the receptor.

CC6.3 The receptor + messenger complex is internalized and ceases to generate a signal.

CC7. Some cells can communicate with neighboring cells electrically; they are electrically coupled.

CC7.1 Electrically coupled cells have gap junctions that span their two membranes.

CC7.2 Current can flow from one cell, when electrically excited, to neighboring cells.

CC7.3 These currents then electrically excite the second cell.