20.1 Signaling Molecules and Cellular Receptors
Hannah Nelson
Learning Objectives
By the end of this section, you will be able to:
- Explain how cellular processes occur through signal, amplification, response
- Describe the general signaling mechanisms linking a ligand to a cellular response
- Recognize the relationship between a ligand’s structure and its mechanism of action
Cells constantly receive and respond to signals from their environment, even from other cells within an organism. These signals, often in the form of ligands, bind to specific receptors on or inside target cells to trigger a range of cellular responses. Characteristics of the signaling molecule determine how the signal reaches its receptor as well as what type of receptor it interacts with. For example, intracellular receptors respond to signals that can pass through the membrane, while cell-surface receptors detect external signals and initiate internal signaling pathways. Together, a coordination of signal, amplification, and response allow cells to facilitate complex processes such as growth, metabolism, and communication.
General Signaling Mechanism
Signals
Signals are molecules in an organism that stimulate cellular processes. In the from a variety of material (hormones, neurotransmitters, amino acids, gasses, etc.) signals are essential for biological processes and are the initiator of cellular events.
Signaling molecules can be either hydrophobic or hydrophilic, and their chemical nature determines how they enter the cell and where they bind. Hydrophobic signaling molecules typically diffuse across the plasma membrane to interact with intracellular receptors. Hydrophilic signaling molecules cannot cross the membrane and instead bind to receptors on the cell surface, triggering intracellular signaling cascades.
Receptors
Receptors are proteins in or on a target cell’s surface that bind to signaling molecules. There are two types of receptors, internal receptors and cell-surface receptors.
Internal receptors, also known as intracellular or cytoplasmic receptors, are found in the cytoplasm of the cell and respond to hydrophobic ligand molecules that are able to travel across the plasma membrane. Some signals upon binding to an internal receptor will induce a conformational change that alters the functionality of that system. Many intracellular receptors are transcription factors that interact with DNA in the nucleus and regulate gene expression.
Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored proteins that bind to external ligand molecules. There are three general categories of cell-surface receptors: ion channel-linked receptors, G-protein coupled receptors (GPCRs), and enzyme-linked receptors. Cell-surface receptors span the plasma membrane and perform signal transduction, in which an extracellular signal is converted into an intercellular signal. Each cell-surface receptor has three main components: an external ligand-binding domain, a hydrophobic membrane-spanning region, and an intracellular domain inside the cell. The ligand-binding domain is also called the extracellular domain. The size and extent of each of these domains vary widely, depending on the type of receptor.
Signal Amplification
Amplification is a crucial part of cellular communication, involving a single signaling event which triggers a signaling cascade that magnifies the initial signal inside the cell. Amplifying a signal often involves second messenger molecules such as cyclic AMP (cAMP), inositol triphosphate (IP3), or calcium ions. Second messengers rapidly increase in concentration after receptor activation. These molecules activate multiple downstream proteins like kinases, which then phosphorylate many target proteins. You can think of this as a signaling domino effect.
Amplification ensures that even a small number of signaling molecules outside the cell can produce a robust and coordinated response internally, enhancing the cell’s sensitivity to external cues and overall cellular efficiency.
Cellular Response
Cellular response refers to the specific actions a cell undertakes once a signal has been processed. These responses can vary from changes in gene expression and protein synthesis to alterations in metabolism, cell shape, or movement. Some responses occur quickly, such as opening ion channels or modifying enzyme activity, while others, like changes in gene transcription, take a more concerted effort over a longer period of time.Cells can regulate the duration and intensity of these responses through feedback mechanisms and signal termination, allowing them to adapt appropriately to their environment and maintain homeostasis.
A critical aspect of cellular signaling is signal termination, which ensures that responses do not continue indefinitely. Without proper termination, continuous signaling can lead to harmful effects, such as uncontrolled cell growth or inappropriate activation of pathways, which can contribute to diseases like cancer. Cells employ various mechanisms to stop signals, including degrading signaling molecules, deactivating receptors, and reversing post-translational modifications. Efficient signal termination allows cells to reset and remain sensitive to new signals, maintaining precise control over cellular functions.
Footnotes
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A. B. Sigalov, The School of Nature. IV. Learning from Viruses, Self/Nonself 1, no. 4 (2010): 282-298. Y. Cao, X. Koh, L. Dong, X. Du, A. Wu, X. Ding, H. Deng, Y. Shu, J. Chen, T. Jiang, Rapid Estimation of Binding Activity of Influenza Virus Hemagglutinin to Human and Avian Receptors, PLoS One 6, no. 4 (2011): e18664.
