Juxtacrine Signaling

12 Key excerpts on "Juxtacrine Signaling"

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  eBook - ePub

  Micro- and Nanoengineering of the Cell Surface

  • Jeffrey M Karp, Weian Zhao(Authors)
  • 2014(Publication Date)
  • William Andrew

    (Publisher)

  Back in 1962, Kauzman and Tanford theorized about the effect of hydrophobicity on protein folding and stability, which was a first step to frame thinking around the emergence of membrane properties. Clearly, things have come a long away since then. The stage is now set for designing membrane engineering strategies with complex, emergent membrane states as a conceptual framework. One can think of surface engineering driven emergence as an overlay on existing, physiologically driven emergent membrane states. From a functional perspective, two pivotal emergent membrane states are the potentials for receptor (inward signal flow) and juxtacrine (outward signal flow) signaling. Attention will now be turned to the latter, in detailing a line of investigation where the early dividends have been flexible cell surface engineering tools and novel therapeutics, and with the ultimate goal of modulating cellular networks now coming into sight.

  1.5 Juxtacrine Signaling and Rewiring Cellular Networks

  Juxtacrine Signaling is a form of intercellular communication that depends on direct interaction of adjoining cells [69 –72] . This cell contact-dependent mode of signaling, typically mediated by paired interactive proteins on apposed cells, is at the heart of diverse biological processes, in particular those requiring tight regulation and spatial control of stimulation of one cell by another (reviewed in Ref. [73] ). The simplest juxtacrine links involve just a pair of interacting cells, for example, an APC interfacing with a T cell of the immune system. The triggering of T-cell receptors by APC-anchored major histocompatibility complex (MHC) antigenic peptide complexes represents a classic two-party juxtacrine signal encounter. Yet, even in this seemingly straightforward situation, greater complexity quickly arises as third-party cells enter the picture, along with an array of paracrine (soluble factor mediated) and more distant endocrine immunomodulatory signals. Thus, juxtacrine intercellular signaling is best thought of in a more encompassing way, as operating within cellular networks of varying complexity that frequently evolve in multistep fashion over varying timescales. Morphogenesis and developmental patterning exemplify how juxtacrine signals can cascade and effect phenotypic changes across a field of cells, with juxtacrine Delta-to-Notch serving as the classical paradigm [74 –78]

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  Physiological Systems in Insects

  • Marc J. Klowden, Subba Reddy Palli, Subba Reddy Pallai(Authors)
  • 2022(Publication Date)
  • Academic Press

    (Publisher)

  Fig. 1.3A ). An example is the prothoracic gland, which during some developmental stages activates its own production of ecdysteroids.

  Fig. 1.3 Types of cell signaling. (A) Autocrine signaling. (B) Contact-dependent signaling. (C) Neuronal signaling. (D) Endocrine signaling. (E) Paracrine signaling. See the text for an explanation.

  Contact-dependent signaling relies on direct contact between neighboring cells, with signaling molecules embedded in the cell membranes or passed directly through pores (Fig. 1.3B ). The signaling cell may produce a molecule that binds to a receptor in the adjacent target cell or release ions that are transferred through gap junctions to trigger a response only in those cells that are in direct contact. Also called 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, which gives 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 (Fig. 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 that 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 (Fig. 1.3D

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  Biology 2e

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

    (Publisher)

  Because of their form of transport, hormones become diluted and are present in low concentrations when they act on their target cells. This is different from paracrine signaling, in which local concentrations of ligands can be very high. Autocrine Signaling Autocrine signals are produced by signaling cells that can also bind to the ligand that is released. This means the signaling cell and the target cell can be the same or a similar cell (the prefix 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. Autocrine signaling also regulates pain sensation and inflammatory 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. In some cases, neighboring cells of the same type are also influenced by the released ligand. In embryological development, this process of stimulating a group of neighboring cells may help to direct the differentiation of identical cells into the same cell type, thus ensuring the proper developmental outcome. Direct Signaling Across Gap Junctions Gap junctions in animals and plasmodesmata in plants are connections between the plasma membranes of neighboring cells. These fluid-filled channels allow small signaling molecules, called intracellular mediators, to diffuse 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 fit through the channels. The specificity of the channels ensures that the cells remain independent but can quickly and easily transmit signals.

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  Advances in Protein Molecular and Structural Biology Methods

  • Timir Tripathi, Vikash Kumar Dubey, Timir Tripathi, Vikash Kumar Dubey(Authors)
  • 2022(Publication Date)
  • Academic Press

    (Publisher)

  14

  3.2: Signaling via cell–cell direct contact or Juxtacrine Signaling

  Cellular communication also occurs through direct cell-to-cell contact where both the receptor and ligand are membrane-bound. It is also known as Juxtacrine Signaling and can occur through three mechanisms: cell-to-cell direct contact, gap junction-mediated signaling, and extracellular matrix (ECM)-mediated signaling. One of the most important examples of Juxtacrine Signaling is the notch-delta signaling pathway. Notch signaling is involved in stem cell fate maintenance and also cell differentiation by the lateral inhibition mechanism.15 Signaling involving the ECM-mediated crosstalk between integrins and actin cytoskeleton controls a wide array of vital cellular functions such as proliferation, migration, apoptosis, and differentiation.16

  4: Cell signaling orchestrates key biological processes

  Cells need to be in constant communication with neighboring cells and the extracellular environment to maintain internal homeostasis, grow, and divide. Signal transduction helps the cells internalize the external cues and carry out effector functions necessary for survival. Signaling controls virtually all the key biological processes of cells, i.e., cell growth, division, differentiation, energy metabolism, migration, and cell death. A signal transduction pathway can regulate one or more of these cellular functions. There are various modes of cell-to-cell communication, depending on the source of the signal received by the cells. Cells can receive messages carried by small molecules, peptides, or proteins secreted by other cells. Cells can also undergo direct physical contact with each other for signaling. They can also receive signals from the extracellular matrix (ECM), where the ECM relays information through mechanical stimuli or ECM-bound molecules. Physical factors, such as heat, light, electrical impulses, and mechanical forces, also activate specific signaling pathways. All these signals activate specific pathways that translate into a change in cell behavior and function. The various modes of signaling and the associated pathways are discussed in the next section.

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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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  Biology for AP® Courses

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

    (Publisher)

  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. Endocrine signals are carried long distances through the bloodstream by hormones, and autocrine signals are received by the same cell that sent the signal or other nearby cells of the same kind. Gap junctions allow small molecules, including signaling molecules, to flow between neighboring cells. Internal receptors are found in the cell cytoplasm. Here, they bind ligand molecules that cross the plasma membrane; these receptor-ligand complexes move to the nucleus and interact directly with cellular DNA. Cell-surface receptors transmit a signal from outside the cell to the cytoplasm. Ion channel-linked receptors, when bound to their ligands, form a pore through the plasma membrane through which certain ions can pass. G-protein-linked receptors interact with a G-protein on the cytoplasmic side of the plasma membrane, promoting the exchange of bound GDP for GTP and interacting with other enzymes or ion channels to transmit a signal. Enzyme-linked receptors transmit a signal from outside the cell to an intracellular domain of a membrane-bound enzyme. Ligand binding causes activation of the enzyme. Small hydrophobic ligands (like steroids) are able to penetrate the plasma membrane and bind to internal receptors. Water-soluble hydrophilic ligands are unable to pass through the membrane; instead, they bind to cell-surface receptors, which transmit the signal to the inside of the cell. 9.2 Propagation of the Signal Ligand binding to the receptor allows for signal transduction through the cell. The chain of events that conveys the signal through the cell is called a signaling pathway or cascade.

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  Mechanotransduction

  Cell Signaling to Cell Response

  • Paul A. Sundaram, Paul Sundaram(Authors)
  • 2020(Publication Date)
  • Academic Press

    (Publisher)

  Gap junctions are transmembranal structures that connect adjacent cells and enable the transport of small molecules and ions (particularly Ca 2+) between neighboring cells. The induction of B cells, which come in direct contact with helper T cells at the threat of antigens in our immune system, is an example of cell communication by direct contact. The secretion of neurotransmitters in the synaptic junctions is an example of another type of cell communication called paracrine signaling where the signaling cell and the target cell are in close proximity to each other but not in direct contact. Fig. 2.1 is a simple illustration of the release of neurotransmitters in the synaptic junction from the presynaptic axon and further transmission of this communication down the line to the proximal postsynaptic axon. Such type of signal is an example of cell communication, in this case, specifically, paracrine signaling, generated frequently in the gastrointestinal tract. Figure 2.1 Typical cell communication. Simple illustration of typical cell cell communication. In the example shown, the release of neurotransmitters from one axon into the synaptic junction of the neighboring axon results in the transmission of a cell signal. The production of hormones by the pituitary gland to accomplish a physiological function far away from the point of release is a third cell communication method known as endocrine signaling. In this case, the hormone, which is the signaling molecule, is released into the bloodstream and travels a relatively long distance to trigger an appropriate response in another cell group much farther away. The distance effect on cell signaling is summarized in Fig. 2.2. Figure 2.2 Cell communication methods. (A) Autocrine signaling illustrating the release of ligands by a cell to be received by its own receptor and accomplish the physiological function of the cell

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  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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  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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  Human Physiology

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

    (Publisher)

  159 CHAPTER 6 Cell Signaling Cell Signaling and Homeostasis • Cell signaling contributes to homeostasis by allowing cells to communicate with one another in order to coordinate body activities. LOOKING BACK TO MOVE AHEAD… • Extracellular fluid, the fluid outside cells, consists of two components: (1) interstitial fluid, the fluid that fills the narrow spaces between cells and (2) plasma, the fluid portion of blood (Section 1.4). • Receptors are proteins that serve as cellular recognition sites; each type of receptor recognizes and is bound by a specific ligand (Section 3.2). • A kinase is an enzyme that adds a phosphate group to a substrate (Section 4.3). • The plasma membrane is highly permeable to nonpolar molecules, such as oxygen (O 2 ) and steroids; moderately permeable to small, uncharged polar molecules, such as water; and impermeable to ions and large, uncharged polar molecules, such as glucose (Section 5.1). Introduction The cells that comprise the body must communicate with each other to coordinate body activities. For example, if you step on a tack, neurons from your foot communicate this painful sensory input to neurons of the spinal cord, which in turn communicate output information to muscle cells of the lower limb that contract to move your foot away from 160 CHAPTER 6 Cell Signaling 6.1 Methods of Cell-to-Cell Communication Objective • Describe the different ways that cells can communicate with one another. There are three general methods of communication between cells: (1) gap junctions, (2) cell-to-cell binding, and (3) extracel- lular chemical messengers. Gap Junctions Electrically Couple Cells Together One way that a cell can communicate with another cell is through gap junctions. At gap junctions, membrane proteins called con- nexins form tunnels called connexons that connect neighboring cells (Figure 6.1a). Through the connexons, ions and small mole- cules can diffuse from the cytosol of one cell to the cytosol of another cell.

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  Biomimetic Materials And Design

  Biointerfacial Strategies, Tissue Engineering And Targeted Drug Delivery

  • Angela Dillow, Anthony Lowman, Angela Dillow, Anthony Lowman(Authors)
  • 2002(Publication Date)
  • CRC Press

    (Publisher)

  Hence, initially recognized extracellular signals are presented internally to provide new feedback signals that can result in release of new extracellular signals. Regulation of this loop is just beginning to be appreciated by the tissue engineering community. Figure 2 Outside-in cell signal transduction: attachment-dependent cells on biomaterials. Many cell-signaling mechanisms and necessary attachment-dependent behaviors are activated by cell–surface attachment. These attachment mechanisms and their resulting signaling phenomena are influenced by adsorbed or insoluble receptor-mediated stimuli on biomaterials surfaces. Soluble protein surface deposition from both extracellular matrix and other serum proteins is known to be influenced by biomaterial surface chemistry. Composition and conformation of the adsorbed protein layer are influenced by surface chemistry and directly affect cell attachment Biomimetic materials and design 164 mechanisms, receptor activation, and resulting signaling pathways through the membrane receptors. Ultimately, cell genetic regulation and phenotypic expression are altered by this mechanism. Hence, some aspects of biomaterials surface chemistry are conveyed through these indirect receptor-mediated pathways, and translated ultimately to genetic regulation and message expression. VIII. MECHANISMS OF SIGNAL TRANSDUCTION THROUGH RECEPTORS Outside-to-inside signal transduction at the cellular level refers to the movement of signals from outside the cell to inside across the cell membrane via specific receptor processing, ultimately ending up in nuclear signaling. Signal movement can be direct, like that associated with receptor molecules of the acetylcholine (nicotinic) class: receptors that constitute ligand-dependent ion channels which, upon external ligand interaction, allow signals to be passed in the form of small ion currents (such as Na + and K + ), either into or out of the cell through the membrane.

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  Cell Signaling

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

    (Publisher)

  1 Introduction to Cell Signaling

  All living cells perceive signals from the outside environment and adjust their behavior accordingly. If you think back to the earliest living cells, it is easy to imagine the incredible pressure they were under to evolve the ability to sense features of the environment and to change in response to these signals. The ability to sense and move toward nutrients, or to sense and avoid stresses and toxins, would give a unicellular organism a huge competitive advantage. This ability to respond to environmental cues is important for single cells, but it is also absolutely essential for the normal development and functioning of multicellular organisms, which depend on a continuous and extensive exchange of information to coordinate the activities of many individual cells. Furthermore, when this cellular communication goes awry, it can result in diseases such as cancer. In this chapter, we will introduce the basic principles of cell signaling and the molecular mechanisms that underlie it.

  What Is Cell Signaling?

  Cells are the smallest fundamental units of life. Part of what makes them so distinctly “living” is their remarkable ability to sense stimuli and to respond to them in a dynamic manner. This ability of cells to detect or receive information and process it to make decisions can also be considered from the broader perspective of information processing. Here we can draw analogies to the engineering and design principles of other, more familiar information-processing systems, such as human- made electronic devices. It is this interface between the unique properties of living systems and the more universal properties of any system that processes information that makes the study of cellular signaling mechanisms so compelling.

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