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Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the Gamma-aminobutyric acid-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

Cell-surface Signaling

JoVE 10877

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects. Cell membrane receptors have three portions: an external ligand-binding domain, a transmembrane domain, and an internal domain. There are three categories of cell membrane receptors based on the consistency of the structure and function of these domains within each category. One category is ligand-gated ion channels which, when bound to a ligand, undergo a conformational change, allowing ions through a channel formed by the transmembrane portion of the receptor. A second category is G-proteins-coupled receptors which have a distinct structure with seven transmembrane domains. Binding of the external domain to a ligand causes the alpha subunit, one of three subunits attached to the internal portion of the receptor, to disassociate from the receptor and create a cellular response. The third category of receptors, the enzyme-linked receptor—also called catalytic receptor

 Core: Biology

What is Cell Signaling?

JoVE 10985

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.

Cells respond to many types of information, often through receptor proteins positioned on the membrane. For example, skin cells respond to and transmit touch information, while photoreceptors in the retina can detect light. Most cells, however, have evolved to respond to chemical signals, including hormones, neurotransmitters, and many other types of signaling molecules. Cells can even coordinate different responses elicited by the same signaling molecule. Typically, cell signaling involves three steps: (1) reception of the signal, (2) signal transduction, and (3) a response. In most signal reception, a membrane-impermeable molecule, or ligand, causes a change in a membrane receptor; however, some signaling molecules, such as hormones, can traverse the membrane to reach their internal receptors. The membrane receptor can then send this signal to intracellular messengers, which transduces the message into a cellular response. This intracellular response may include a change transcription, translation, protein activation,

 Core: Biology

Receptor-mediated Endocytosis

JoVE 10708

Receptor-mediated endocytosis is a process through which bulk amounts of specific molecules can be imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle and give it its round form. One well-characterized example of receptor-mediated endocytosis is the transport of low-density lipoproteins (LDL cholesterol) into the cell. LDL binds to transmembrane receptors on the cell membrane. Adapter proteins allow clathrin to attach to the inner surface of the membrane. These protein complexes bend the membrane inward, creating a clathrin-coated vesicle inside the cell. The neck of the endocytic vesicle is pinched off from the membrane by a complex of the protein dynamin and other accessory proteins. The endocytic vesicle fuses with an early endosome, and the LDL dissociates from the receptor proteins due to a lower pH environment. Empty receptor proteins are separated into transport vesicles to be re-inserted into the outer cell membrane. LDL remains in the endosome, which binds with a lysosome. The lysosome provides digestive enzymes that break up LDL into free cholesterol that can be used by the cell. There ar

 Core: Biology


JoVE 10853

When we hear a sound, our nervous system is detecting sound waves—pressure waves of mechanical energy traveling through a medium. The frequency of the wave is perceived as pitch, while the amplitude is perceived as loudness.

Sound waves are collected by the external ear and amplified as they travel through the ear canal. When sounds reach the junction between the outer and middle ear, they vibrate the tympanic membrane—the eardrum. The resulting mechanical energy causes the attached ossicles—a set of small bones in the middle ear—to move. The ossicles vibrate the oval window, the outermost part of the inner ear. In the labyrinth of the inner ear, the sound wave energy is transferred to the cochlea—a coiled structure in the inner ear—causing the fluid within it to move. The cochlea contains receptors that transduce mechanical sound waves into electrical signals that can be interpreted by the brain. Sounds within the hearing range vibrate the basilar membrane in the cochlea and are detected by hair cells on the organ of Corti, the site of transduction. Along the primary auditory pathway, the signals are sent through the auditory nerve to the cochlear nuclei in the brainstem. From here, they travel to the inferior colliculus of the midbrain and up to the thalamus, and then to the primary auditory cortex. Along this pat

 Core: Biology

Photoreceptors and Plant Responses to Light

JoVE 11115

Light plays a significant role in regulating the growth and development of plants. In addition to providing energy for photosynthesis, light provides other important cues to regulate a range of developmental and physiological responses in plants.

What Is a Photoreceptor?

Plants respond to light using a unique set of light-sensitive proteins called photoreceptors. Photoreceptors contain photopigments, which consist of a protein component bound to a non-protein, light-absorbing pigment called the chromophore. There are several different types of photoreceptors, which vary in their amino acid sequences and the type of chromophore present. These types maximally respond to different specific wavelengths of light, ranging from ultraviolet B (280-315 nanometers) to far-red (700-750 nanometers). The chromophore's absorption of light elicits structural changes in the photoreceptor, triggering a series of signal transduction events that result in gene expression changes. The Phytochrome System Many types of photoreceptors are present in plants. Phytochromes are a class of photoreceptors that sense red and far-red light. The phytochrome system acts as a natural light switch, allowing plants to respond to the intensity, duration, and color of environmental light. The phytochrome system plays a s

 Core: Biology


JoVE 10860

Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively non-selective cation permeability. There are at least three types of receptors that are activated by cold, of which TRPM8 and TRPA1 are particularly sensitive. TRPM8 has a temperature sensitive range of about 10-26 oC (50-79 oF), and is largely associated with the perception of non-painful, or innocuous, cold. Menthol, a compound found in mint leaves, can also activate this receptor, which helps explain why this flavor is often perceived as cool. When temperatures are low enough to feel painful (i.e., noxious cold), TRPA1 receptors are activated. TRPA1 receptors respond to any temperature lower than 17 oC (~63 oF). There are at least seven receptors that respond to heat. Of these, five respond to temperatures in the innocuous warmth range: TRPM2 (23-38 oC, or ~73-100oF), TRPC5 (26-38 oC, or ~79-

 Core: Biology

The Cochlea

JoVE 10855

The cochlea is a coiled structure in the inner ear that contains hair cells—the sensory receptors of the auditory system. Sound waves are transmitted to the cochlea by small bones attached to the eardrum called the ossicles, which vibrate the oval window that leads to the inner ear. This causes fluid in the chambers of the cochlea to move, vibrating the basilar membrane.

The basilar membrane extends from the basal end of the cochlea near the oval window to the apical end at its tip. Although the cochlea itself narrows towards the apical end, the basilar membrane has the opposite geometry—becoming wider and more flexible towards the apical end. Primarily because of these physical characteristics, the apical end of the basilar membrane maximally vibrates when exposed to low-frequency sounds, while the narrower, stiffer basal end maximally vibrates when exposed to high frequencies. This gradient of frequency response creates tonotopy—a topographic map of pitch—in the cochlea. The hair cells are stimulated by the shearing force created by the vibration of the basilar membrane below them, relative to the stiffer tectorial membrane above them. Because of the tonotopy of the basilar membrane, hair cells are maximally stimulated by different frequencies depending on where they are in the cochlea. Those at the basal end respond be

 Core: Biology

RNA Splicing

JoVE 10802

The process in which eukaryotic RNA is edited prior to protein translation is called splicing. It removes regions that do not code for proteins and patches the protein-coding regions together. Splicing also allows several protein variants to be expressed from a single gene and plays an essential role in development, tissue differentiation, and adaptation to environmental stress. Errors in splicing can lead to diseases such as cancer. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts designated to become mRNA are called precursor messenger RNA (pre-mRNA). The pre-mRNA is then processed to form mature mRNA that is suitable for protein translation. Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins whereas introns are the non-coding regions. RNA splicing is the process by which introns are removed and exons patched together. Splicing is mediated by the spliceosome—a complex of proteins and RNA called small nuclear ribonucleoproteins (snRNPs). The spliceosome recognizes specific nucleotide sequences at exon/intron boundaries. First, it binds to a GU-containing sequence at the 5’ end of the intron and to a branch point sequence containing an A towards the 3’ end of the intron. In a number of carefully-orches

 Core: Biology

Enzyme-linked Receptors

JoVE 10723

Enzyme-linked receptors are proteins which act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.

RTKs are also called neurotrophin (NT) receptors because they bind nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, NT-4/5, NT-6, and NT-7. The growth factors typically bind to an RTK subfamily of tropomyosin-related kinase receptors (Trk): Trk A, Trk B, and Trk C. Trk A is specific for NGF, NT-6, and NT-7. Trk B binds BDNF and NT-4/5, while Trk C is specific for NT-3. NT-3 can also bind with low affinity to Trk A and TrkB. The Trk receptors have a single transmembrane domain, with a growth factor binding site on the extracellular portion and an enzyme activation site intracellularly. Trk receptors can be monomeric or dimerized, where two Trk receptors are bound together. To activate the receptor, a single growth factor molecule either binds two monomeric receptors, causing them to dimerize, or it binds both sites on a pre-dimerized receptor. Once the receptors are bound, the tyrosines phosphorylate by pulling phosphates from ATP and donating them to each other, a process called “autophosphorylation.” This opens docking sites along the i

 Core: Biology
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