Paracrine Signaling

11 Key excerpts on "Paracrine Signaling"

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  eBook - ePub

  Physiological Systems in Insects

  • Marc J. Klowden, Marc J Klowden(Authors)
  • 2013(Publication Date)
  • Academic Press

    (Publisher)

  juxtacrine signaling , this is the fastest mode of communication and can be found in cardiac muscle cells whose contractions are coordinated, allowing these to occur simultaneously. Contact-dependent signaling also occurs during early development, giving adjacent cells information about their location relative to other cells, and can specify their developmental fate.

  Neuronal signaling delivers messages across long distances within the organism to specific cells. As described in Chapter 11 , a signaling neuron sends an electrical signal along its axon that triggers the release of a neurotransmitter at its synapse with a target cell (Figure 1.3C ). The neurotransmitter binds to postsynaptic receptors in target cells, causing a physiological response in those cells. The speed of transmission is rapid, but depends on the physical distance over which the signal must travel.

  Paracrine and endocrine signaling both involve the diffusion of signal molecules through an extracellular medium. Endocrine signaling is the most public, releasing hormones into the blood that are distributed to all cells of the body (Figure 1.3D ). Only those cells with receptors that recognize the hormone are capable of responding. The signaling cells may consist of endocrine cells or more specialized neurosecretory cells. Some endocrine signaling molecules are hydrophobic and are able to cross the cell membrane and bind to internal receptor proteins, but most others are peptides that must remain outside and bind to external receptors.

  Paracrine Signaling is more intimate, with the signal molecules diffusing not through the blood but through the extracellular matrix instead (Figure 1.3E ). The proteins secreted by the target cells are effective over only a short distance and induce changes only in neighboring cells that bear specific receptors localized in regions of cytoplasmic extensions called cytonemes

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  Karp's Cell and Molecular Biology

  • Gerald Karp, Janet Iwasa, Wallace Marshall(Authors)
  • 2021(Publication Date)
  • Wiley

    (Publisher)

  On the other hand, insights into cell signaling can tie together a variety of seemingly independent cellular processes. Cell signaling is also intimately involved in the regulation of cell growth and division. This makes the study of cell signaling crucially important for understanding how a cell can lose the ability to control cell division and develop into a malignant tumor. It may be helpful to begin the discussion of this complex subject by describing a few of the general features that are shared by most signaling pathways. Cells usually communicate with one another through extracellular messenger molecules. Extracellular messengers can travel a short distance and stimu- late cells that are in close proximity to the origin of the message, or they can travel throughout the body, potentially stimulating cells that are far away from the source. In the case of autocrine signaling, the cell that is producing the messenger expresses receptors on its surface that can respond to that messenger (Figure 15.1a). Consequently, cells releasing the message will stimulate (or inhibit) themselves. During Paracrine Signaling (Figure 15.1b), messenger molecules travel only short distances through the extracellular space to cells that are in close prox- imity to the cell generating the message. Paracrine messenger molecules are usually limited in their ability to travel around the body because they are inherently unstable, or they are degraded by enzymes, or they bind to the extracellular matrix. Finally, during endocrine signaling, messenger molecules reach their target cells via passage through the bloodstream (Figure 15.1c). Endocrine messengers, also called hormones, typically act on target cells located at distant sites in the body. An overview of cellular signaling pathways is depicted in Figure 15.2. Cell signaling is initiated with the release of a mes- senger molecule by a cell that is engaged in sending messages to other cells in the body (step 1, Figure 15.2).

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  eBook - ePub

  Biochemistry of Signal Transduction and Regulation

  • Gerhard Krauss(Author)
  • 2014(Publication Date)
  • Wiley-VCH

    (Publisher)

  The hormone reaches the target cells from the hormone-producing cell by passive diffusion. The producing cell must be found in the vicinity of the receiving cells for this type of communication. The signaling is rather local, and the participating signaling molecules are sometimes termed tissue hormones or local mediators. One special case of paracrine signal transduction is that of synaptic neurotransmission, in which a nerve cell communicates with either another nerve cell or with a muscle cell. 1.3.3.3 Autocrine Signaling In autocrine signaling, cells of the same type communicate with one another. The hormone produced by the signaling cell affects a cell of the same type by binding to receptors on these cells, initiating an intracellular signal cascade. If an autocrine hormone is secreted simultaneously by many cells, then a strong response is triggered. Autocrine mechanisms are of particular importance in the immune response. 1.3.4 Direct Protein Modification by Signaling Molecules A special case of intercellular signaling is represented by a class of small, reactive signaling molecules, such as nitric oxide (NO; see Section 8.10). NO is synthesized in a cell in response to an external signal and is delivered to the extracellular fluid. NO reaches neighboring cells either by diffusion or in a protein-bound form, and a modification of the target enzymes ensues which results in a change in the activity of these enzymes. NO is characterized as a mediator that lacks a receptor in the classical sense. 1.4 Intracellular Signaling: Basics External signals such as hormones, sensory signals or electrical signals are specifically recognized by receptors that transduce the external signal into an intracellular signaling chain

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  Biology 2e

  • Mary Ann Clark, Jung Choi, Matthew Douglas(Authors)
  • 2018(Publication Date)
  • Openstax

    (Publisher)

  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 another specific molecule, in some cases, delivering a signal in the process. Ligands can thus be thought of as signaling molecules. Ligands interact with proteins in target cells, which are cells that are affected by chemical signals; these proteins are also called receptors. Ligands and receptors exist in several varieties; however, a specific ligand will have a specific receptor that typically binds only that ligand. Forms of Signaling There are four categories of chemical signaling found in multicellular organisms: Paracrine Signaling, endocrine signaling, autocrine signaling, and direct signaling across gap junctions (Figure 9.2). The main difference between the different categories of signaling is the distance that the signal travels through the organism to reach the target cell. We should note here that not all cells are affected by the same signals. 252 Chapter 9 | Cell Communication This OpenStax book is available for free at http://cnx.org/content/col24361/1.8 Figure 9.2 In chemical signaling, a cell may target itself (autocrine signaling), a cell connected by gap junctions, a nearby cell (Paracrine Signaling), or a distant cell (endocrine signaling). Paracrine Signaling acts on nearby cells, endocrine signaling uses the circulatory system to transport ligands, and autocrine signaling acts on the signaling cell. Signaling via gap junctions involves signaling molecules moving directly between adjacent cells. Paracrine Signaling Signals that act locally between cells that are close together are called paracrine signals. Paracrine signals move by diffusion through the extracellular matrix. These types of signals usually elicit quick responses that last only a short period of time.

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  Biology for AP® Courses

  • Julianne Zedalis, John Eggebrecht(Authors)
  • 2018(Publication Date)
  • Openstax

    (Publisher)

  neurotransmitter paracrine signal phosphatase phosphodiesterase quorum sensing receptor second messenger signal integration signal transduction signaling cell signaling pathway synaptic signal target cell chemical ligand that carries a signal from one nerve cell to the next signal between nearby cells that is delivered by ligands traveling in the liquid medium in the space between the cells enzyme that removes the phosphate group from a molecule that has been previously phosphorylated enzyme that degrades cAMP, producing AMP, to terminate signaling method of cellular communication used by bacteria that informs them of the abundance of similar (or different) bacteria in the environment protein in or on a target cell that bind to ligands small, non-protein molecule that propagates a signal within the cell after activation of a receptor causes its release interaction of signals from two or more different cell-surface receptors that merge to activate the same response in the cell propagation of the signal through the cytoplasm (and sometimes also the nucleus) of the cell cell that releases signal molecules that allow communication with another cell (also signaling cascade) chain of events that occurs in the cytoplasm of the cell to propagate the signal from the plasma membrane to produce a response chemical signal (neurotransmitter) that travels between nerve cells cell that has a receptor for a signal or ligand from a signaling cell CHAPTER SUMMARY 9.1 Signaling Molecules and Cellular Receptors Cells communicate by both inter- and intracellular signaling. Signaling cells secrete ligands that bind to target cells and initiate a chain of events within the target cell. The four categories of signaling in multicellular organisms are Paracrine Signaling, endocrine signaling, autocrine signaling, and direct signaling across gap junctions. Paracrine Signaling takes place over short distances.

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  No longer available |Learn more

  Cell Signaling

  • Wendell A. Lim, Wendell Lim, Bruce Mayer, Tony Pawson(Authors)
  • 2014(Publication Date)
  • Garland Science

    (Publisher)

  6 Chapter 1 Introduction to Cell Signaling THE FUNDAMENTAL ROLE OF SIGNALING IN BIOLOGICAL PROCESSES Our current understanding of signaling mechanisms is the result of many years of research in seemingly unrelated fields, using an array of different experimental approaches. It is really only recently, with the remarkable advances in our ability to identify, clone, and sequence key genes involved in a process, that we have discovered that the same or closely related types of communication molecules are utilized in a wide range of physi-ological information-processing functions. This synthesis, which has led to the emergence of the field of cell signaling, is one of the major scientific accomplishments of the last few decades. Work in many different fields converged to reveal the underlying mechanisms of signaling The field of cell signaling emerged from a number of disciplines that have historically been considered distinct ( Figure 1.3 ). Indeed, the diversity of areas of inquiry that ultimately led to the field of cell signaling under-lines the central role of signaling across biology. For example, because signaling is so important to normal physiology, the disruption or misregu-lation of signaling mechanisms is the basis for many human diseases, and thus these mechanisms are of interest in the areas of medicine and human health. Similarly, because normal development depends on the precise coordination of cell behaviors such as differentiation and move-ment, research on developmental events necessarily sheds light on the underlying signaling mechanisms. And because the signaling apparatus is comprised of biomolecules such as proteins, which are encoded by the genetic material, signaling mechanisms are amenable to the experimen-tal approaches and analytic tools of biochemistry and genetics.

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  eBook - ePub

  Volatile Biomarkers for Human Health

  From Nature to Artificial Senses

  • Hossam Haick(Author)
  • 2022(Publication Date)
  • Royal Society of Chemistry

    (Publisher)

  Part 2: Communication: Volatile Biomarkers as a Signaling Agents Passage contains an image Chapter 9 Signal Transfer and Transduction between Cells

  Mamatha Serasanambatia , Dina Hashoul,b and Hossam Haick,b

  a a Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA;

  b Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa 3200003, IsraelEmail: [email protected]

  9.1 Introduction

  Cell-to-cell communication has a critical role during tumor development and progression, allowing cancer cells to reprogram the surrounding tumor microenvironment and cells located at distant sites.

  1 ,2

  Cells communicate by several means, nonetheless, with broadly three types of cell communication: autocrine, paracrine and juxtacrine signaling.3 In autocrine signaling, a cell secretes a chemical messenger and has the cognate receptor, thereby allowing it to communicate with itself and other cells of the same type. Paracrine Signaling involves at least two types of cells: one cell type without the cognate receptor secretes a chemical message, whereas another cell type has the cognate receptor but does not secrete the biomolecule. Lastly, juxtacrine signaling involves two cells in which one cell has a membrane-bound ligand that binds to its cognate receptor on another cell.

  2 –5

  Proteomic and genomic approaches have been the main approaches to study signaling communication in cell proliferation, migration, cell recognition and differentiation.6 Though tremendous advances have been achieved, several limitations restrict the fulfilment of approaches to diagnosis and therapeutic applications. These limitations include but are not confined to:

  5 –9

  (1) proteomics and genomics requiring prior and accurate knowledge of specific genes or proteins, exclusive to in vitro and in vivo trials – something that does not necessarily reflect real-life situations; and (2) genomics and proteomics, which continue to be expensive and of low specificity and which require complex analytical algorithms that are prolonged and cumbersome. Since cancer is a systematic disease (polygenetic) that involves several mutations at different sites8 (genetic, epigenetic, local to or at a distance from the primary tumor, etc.

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  Extracellular and Intracellular Signaling

  • James D Adams, Keith Parker(Authors)
  • 2011(Publication Date)
  • Royal Society of Chemistry

    (Publisher)

  4,5 11.2.1 Types of Signaling Any signaling network or cascade is a series of biochemical processes, where each process is initiated by the appearance of a signal which is followed by its sensing, processing and transmission as another signal or signals for the next downstream process in the signaling cascade. The signal may appear either inside or outside the cell for processing. Extracellular signals are usually sensed and processed by plasma membrane proteins. Intracellular signals are pro-cessed by soluble proteins or membrane proteins in the plasma membrane or those on the surface or cell organelles. The spatio-temporal separation of signaling processes and cascades men-tioned earlier allows one to classify signaling processes into the following types that depend on the spatial origin of the signal in an organism and its reach within the organism: a) Endocrine signaling: In this long-range signaling, signal molecules such as hormones are released by a cell and travel long distances ( via bloodstream in animals or vascular system in plants) to cause an effect in a different part of the organism. Processing of sensory signals like light, taste and smell can also be considered endocrine. b) Paracrine Signaling: This is a short-range version of endocrine signaling, where the signal produced by a cell is sensed locally, e.g. neuro-transmitters that are processed by proximal neurons. c) Juxtacrine signaling: In this signaling process, the signal is membrane bound on one cell and is sensed by a receptor on the adjacent cell, 190 Chapter 11 e.g. membrane proteins on a cell membrane can be sensed by a Notch protein on the neighboring cell. d) Autocrine signaling: In this signaling process, cells release a signal mole-cule outside the cell, which is sensed by a membrane protein on the same cell leading to self-stimulation, e.g. breast cancer cells release transform-ing growth factor alpha (TGF-a ) that interact with its epidermal growth factor (EGF) receptor.

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  Human Physiology

  • Bryan H. Derrickson(Author)
  • 2019(Publication Date)
  • Wiley

    (Publisher)

  An action potential is a form of long-distance communication because it spreads along the membrane of the entire length of the axon, which can be very long (a meter or more) in many neurons. Graded poten- tials and action potentials are examined further in Chapter 7 (see Section 7.3). Local Mediators Local mediators, also known as local regulators or local agents, are extracellular chemical messengers that act on nearby target cells without entering the bloodstream (Figure 6.3c). They are released from a cell into interstitial fluid and then diffuse through the fluid to act locally on neighboring cells or on the same cell that secreted them. Local mediators that act on neighboring cells are called paracrines (para- = beside or near), and those that act on the same cell that secreted them are called autocrines (auto- = self). Cell signaling that occurs through local mediators is called local signaling. Because of the close proximity of the local mediator and the target cell, local signaling is a type of short-distance communication. Synaptic signaling is actually a form of local signaling, with neurotransmitters functioning as paracrines. However, synaptic signaling is considered to be in its own category because it is a form of communication that specifically occurs between a neuron and a postsynaptic cell. Examples of local mediators include cytokines, nitric oxide, eicosanoids, and growth factors. Cytokines An important group of local mediators in the body is the cytokines, molecules that regulate many cell functions, including cell growth and differentiation. An exam- ple of a cytokine is interleukin-2 (IL-2), which is released by helper T cells (a type of white blood cell) during immune responses (see Chapter 17). IL-2 helps activate other nearby immune cells, a paracrine effect. It also acts as an autocrine by stimulating the same cell that released it to proliferate.

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  Lecture Notes

  Human Physiology

  • Ole H. Petersen(Author)
  • 2019(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Cells communicate with one another by chemical signals that either diffuse between cells (neurotransmitters, and paracrine and autocrine agents), or are disseminated in the blood (hormones). These signals include small organic molecules (e.g. acetylcholine and adrenaline), and larger molecules such as proteins and steroids. Cells may also communicate with their immediate neighbours through gap junctions, which transmit both electrical and chemical signals.

  Chemical signalling

  The nervous and endocrine systems use chemical signals, neurotransmitters and hormones, respectively, for communication. Neurotransmitters are released from neurones, diffuse across a narrow synaptic space or cleft (<100 nm) and act on adjacent neurones, muscle cells or secretory cells in glands; hormones are transmitted in the circulation and act on cells of distant target organs. Hormones act at very low concentrations, typically 10−6 to 10−9 mol L−1 (but in some cases as low as 10−12 mol L−1 ), while the concentrations of neurotransmitters in synaptic clefts may reach 5 × 10−4 mol L−1 (e.g. acetylcholine at the neuromuscular junction). In addition there are paracrine agents released locally by cells that act on neighbouring cells and autocrine agents that act on the cells that produced them. Therefore neurotransmitters, by definition, are paracrine agents, although they are not usually classified as such, and some hormones, e.g. gastrointestinal hormones, may also be classified as paracrine agents, because they may act locally as well as travelling in the blood stream to distant target organs. Secretions of neurones that are transported to distant target organs in the blood stream are referred to as neurohormones. Finally, certain cells secrete growth factors that are essential at critical stages in the development of their target cells.

  Chemical signals may be ions or metabolites (e.g. Ca2+ , glucose or amino acids) which stimulate certain endocrine cells; they may be simple organic molecules (e.g. the neurotransmitters acetylcholine, noradrenaline and glutamate), or they may be more complex molecules (e.g. protein and steroid hormones). Even dissolved gases such as nitric oxide and carbon monoxide may act as chemical signals between cells. Many substances that were first identified as hormones produced in endocrine glands are also synthesized in the nervous system where they act as neurotransmitters or neuromodulators (see Chapter 3

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  Molecular, Cellular, and Tissue Engineering

  • Joseph D. Bronzino, Donald R. Peterson(Authors)
  • 2018(Publication Date)
  • CRC Press

    (Publisher)

  For example, signaling proteins are highly modular in function and are comprised of evo-lutionarily conserved domains that provide binding and enzymatic properties (Pawson 2004). This is analogous to engineered networks—every chemical refinery may be different, but each is built from the same fundamental parts list (chillers, evaporators, reactors, etc.). Several excellent reviews of signaling-protein modules are available in the literature (Seet et al. 2006; Yaffe 2002; Yaffe and Elia 2001); therefore, we do not cover the topic here. We instead take a higher-level view in this chapter, focusing on systems principles of signaling networks that have repeatedly been shown to impact cell-fate choice. Two biological themes stood out because of their recognized impor-tance and complexity: (1) inducible autocrine–paracrine factors and (2) signaling dynamics, and we dedicate sections to each (Figure 31.1b and c). At the end of the chapter, we discuss how computational models have played an important role in defining network-level principles of signal transduction (Figure 31.1d). Many of the published examples we discuss are theoretical. However, as techniques for measur-ing signal-transduction networks become more advanced, we predict that models will soon become essential for understanding signaling data more fully (Janes and Yaffe 2006b). Only by the combination of modeling and experiment do we stand a chance at understanding the coordination of cell choice. 31.2 Autocrine and Paracrine Signaling in Cell-Fate Determination Extracellular stimuli initiate cascades of intracellular signaling activity. The binding of an extracellular ligand to its target cell-surface receptor activates intracellular signaling pathways that ultimately dic-tate the cell’s response. Signals are transduced along enzymatic pathways through a complex network of interactions from the cell surface to the nucleus, leading to changes in gene transcription and cell behavior.

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