Attracting Abundance

- 105 -

The Law

Belief - XVII

Our Cellular Biology - XVI

Because membrane receptors interact with both extra-cellular signals and molecules within the cell, they permit signaling molecules to affect cell function without actually entering the cell.. This is important because most signaling molecules are either too big or too charged to cross a cell's plasma membrane.

Not all receptors exist on the exterior of the cell. Some exist deep inside the cell, or even in the nucleus.These receptors typically bind to the signal molecules that can pass through the plasma membrane, such as gases like nitrous oxide and steroid hormones like estrogen.

The ability of cells to perceive and correctly respond to their micro-environment is the basis of development, tissue repair, and immunity as well as normal tissue homeostasis. Errors in cellular information processing are responsible for diseases such as cancer, autoimmunity, and diabetes.

Once a receptor protein receives a signal, it undergoes a conformational change, which in turn release a series of biochemical reactions within the cell. These intra-cellular signaling pathways, also called signal tansduction cascades, typically amplify the message, producing multiple intra-cellular signals for every one receptor that is bound.

Note: Signal-transduction cascades mediate the sensing and processing of stimuli. These molecular circuits detect, amplify, and integrate diverse external signals to generate responses such as changes in enzyme activity, gene expression, or ion-channel activity.

An environmental signal, such as a hormone, is first received by interaction with a cellular component, most often a cell-surface receptor. The information that the signal has arrived is then converted into other chemical forms, or transduced. The signal is often amplified before evoking a response. Feedback pathways regulate the entire signaling process. For those who are interested in knowing the cell signalling in a little more detail, continue reading the note. The process of cell signalling are as follows:

1: Membrane receptors transfer information from the environment to the cell's interior. A few nonpolar signal molecules such as estrogens and other steroid hormones are able to diffuse through the cell membranes and, hence, enter the cell. Once inside the cell, these molecules can bind to proteins that interact directly with DNA and modulate gene transcription. Thus, a chemical signal enters the cell and directly alters gene-expression patterns. However, most signal molecules are too large and too polar to pass through the membrane, and no appropriate transport systems are present. Thus, the information that signal molecules are present must be transmitted across the cell membrane without the molecules themselves entering the cell. A membrane-associated receptor protein often performs the function of information transfer across the membrane. Such a receptor is an intrinsic membrane protein that has both extracellular and intracellular domains. A binding site on the extracellular domain specifically recognizes the signal molecule (often referred to as the ligand). The interaction of the ligand and the receptor alters the structure of the receptor, including the intracellular domain. These structural changes are not sufficient to yield an appropriate response, because they are restricted to a small number of receptor molecules in the cell membrane. The information embodied by the presence of the ligand, often called the primary messenger, must be transduced into other forms that can alter the biochemistry of the cell.

2: Second messengers relay information from the receptor-ligand complex. Activation of the receptors causes synthesis of small molecules called second messenger. Changes in the concentration of second messengers, constitute the next step in the molecular information circuit. 

The use of second messengers has several consequences. First, second messengers are often free to diffuse to other compartments of the cell, such as the nucleus, where they can influence gene expression and other processes. Second, the signal may be amplified significantly in the generation of second messengers. Enzymes or membrane channels are almost always activated in second-messenger generation; each activated macromolecule can lead to the generation of many second messengers within the cell. Thus, a low concentration of signal in the environment, even as little as a single molecule, can yield a large intracellular signal and response. Third, the use of common second messengers in multiple signaling pathways creates both opportunities and potential problems. Input from several signaling pathways, often called cross talk, may affect the concentrations of common second messengers. Cross talk permits more finely tuned regulation of cell activity than would the action of individual independent pathways. However, inappropriate cross talk can cause second messengers to be misinterpreted.

3: The signal is terminated. After a signaling process has been initiated and the information has been transduced to affect other cellular processes, the signaling processes must be terminated. Without such termination, cells lose their responsiveness to new signals. Moreover, signaling processes that fail to be terminated properly may lead to uncontrolled cell growth and the possibility of cancer.

Refer to the figure alongside for a pictorial depiction of the signaling process. This signal transduction cascade involves molecules outside the cell, inside the cytoplasm, and inside the nucleus. Membranes separate these three areas. At the top of the diagram, a plasma membrane is shown as a horizontal phospholipid bilayer. Each phospholipid is represented as a green circle with two purple tails hanging vertically from it. The top layer of phospholipids is oriented with the green circle on the extracellular surface and the purple tails hanging downward, and the bottom layer of phospholipids is oriented with the green circles on the intracellular surface and the purple tails pointing upward, where they meet the tails from the top layer. In the extracellular space above the plasma membrane, a downward pointing arrow shows an adrenaline molecule (purple sphere) binding to an adrenergic receptor (receptors which attract adernaline signal molecules). The adrenergic receptor is depicted as a lighter purple, snake-like structure that starts out on the left-hand side on the extracellular face and spans the plasma membrane seven times, making a U-turn after it crosses the membrane each time. The receptor has a small U-shaped cup, representing the adrenaline-binding site, located at its far left side on its extracellular face. The adrenergic receptor is activated following adrenaline binding, and this activation is indicated by a yellow sun-like structure associated with the third loop on the adrenergic receptor's intracellular face. Within the cytoplasm, the adrenergic receptor continues the signaling cascade. The intracellular tail of the receptor at the far right is shown to be associated with inactive G-protein molecules, represented by an orange, irregular-shaped beta subunit on the left, a purple, irregular-shaped alpha subunit in the middle, and a long, thin, green gamma subunit on the far right. A GDP molecule (light purple square) is shown bound to the alpha subunit. The alpha subunit interacts with both the beta and gamma subunits. Thin regions of the beta and gamma subunits extend upward and are anchored in the plasma membrane where they associate with each other. Following adrenaline binding to the adrenergic receptor, the G-protein is activated, and the beta and gamma subunits dissociate from the alpha subunit. After activation, the alpha subunit is shown anchored in the plasma membrane by a long, thin tail, and its bound GDP molecule has been replaced with a GTP molecule (dark purple square). The activated alpha subunit is now associated with adenylyl cyclase, which is represented as a thick, green, U-shaped structure that spans the plasma membrane.The activation of adenylyl cyclase is represented by a yellow sun-like structure on its right, intracellular face. Adenylyl cyclase converts ATP (green oval) into cyclic AMP molecules (red circles). The cyclic AMP then stimulates the conversion of inactive protein kinase A (PKA), which is depicted as a light blue triangle, into activated PKA, which is depicted as a four-sided diamond with a yellow sun-like structure attached to the bottom of it. The signaling cascade moves to the nucleus when the activated PKA enters the nucleus through a nuclear pore complex, which is shown as a gap between two nuclear membranes. A black arrow points downward from the activated PKA to show it stimulating the phosphorylation of an inactive transcription factor. Once the transcription factor is phosphorylated,it is active. The active form of the transcription factor has a small, round, blue phosphate group attached to its right side. A double-stranded, helical DNA molecule is shown below the activated transcription factor. The DNA is grey-colored at each end and has a gold central region labeled as the activated target  gene. A vertical black arrow points downward from the target gene to a blue mRNA molecule and is labeled to show that the phosphorylated transcription factor stimulates the transcription of the target gene.

How do signals affect cell function? Protein kinases (an enzyme that catalyses the transfer of a phosphate group from ATP to a specified molecule), such as PKA and PKC, catalyze the transfer of phosphate groups from ATP molecules (ATP is a high-energy molecule found in every cell. Its job is to store and supply the cell with needed energy) to protein molecules. These phosphorylation reactions ( Phosphorylation is the addition of a phosphate group (PO₄³⁻) to a molecule) control the activity of many enzymes involved in intracellular signaling pathways. Specifically, the addition of phosphate groups causes a conformational change in the enzymes, which can either activate or inhibit the enzyme activity. Then, when appropriate, protein phosphatases remove the phosphate groups from the enzymes, thereby reversing the effect on enzymatic activity.

Phosphorylation allows for intricate control of protein function. Phosphate groups can be added to multiple sites in a single protein, and a single protein may in turn be the substrate for multiple kinases and phosphatases.

At any one time, a cell is receiving and responding to numerous signals, and multiple signal transduction pathways are operating in its cytoplasm. Many points of intersection exist among these pathways. For instance, a single second messenger or protein kinase might play a role in more than one pathway. Through this network of signaling pathways, the cell is constantly integrating all the information it receives from its external environment. 

To summarise, cells typically receive signals in chemical form via various signaling molecules. When a signaling molecule joins with an appropriate receptor on a cell surface, this binding triggers a chain of events that not only carries the signal to the cell interior, but amplifies it as well. Cells can also send signaling molecules to other cells. Some of these chemical signals — including neurotransmitters — travel only a short distance, but others must go much farther to reach their targets.

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2008 USA Women's U-20 Match Issue World Cup Home Shirt Washington #16

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Condition of shirt - Excellent

Size - Women's Medium

Condition details - Bright colors, badges, printing and sleeve patch are great, a few tiny faint pulls to reverse

Made by - Nike

Player - Forward Nikki Washington #16

Player shirt features - Correct size and style plastic material printing professionally heat pressed, correct felt Chile 2008 FIFA U-20 Women's World Cup patch to sleeve, some areas of the design are heat bonded

Notes - Rare player shirt believed to have been issued to or worn by Washington for a match at the 2008 Women's U-20 World Cup, held in Chile. The forward started all but one of the USA's matches at the tournament, including 65 minutes in the Final, where the side overcame North Korea 2-1 to claim the trophy