Intro To Cellular Communication

• Autocrine signaling: This type of signaling occurs when a cell releases signaling molecules (ligands) that bind to receptors on its own surface. As a result, the cell modifies its behavior or activity based on this self-generated signal. This mechanism is crucial for processes such as cell growth and self-regulation.

• Paracrine signaling: In this scenario, signaling molecules are released by cells and affect nearby, neighboring cells. This form of communication is vital for local cellular responses, especially in immune responses, tissue repair, and during development. It allows for a quick and effective response from surrounding cells without affecting distant ones.

• Endocrine signaling: This is characterized by the long-range transmission of signals through the bloodstream. Endocrine cells release hormones, which travel throughout the body to reach target cells that have specific receptors for these hormones. This type of signaling is essential for regulating various bodily functions, including metabolism, growth, and mood.

Regardless of the type of communication, receptor proteins and ligands are designed with specific chemical structures that enable them to interact selectively. This specificity ensures that different receptors respond uniquely to different ligands, allowing for a complex web of cellular signaling.

Signal Transduction

Cells need to undergo physiological changes in response to environmental stimuli to survive in a constantly changing landscape. Signal transduction is critical to this process, as it allows cells to interpret external signals and trigger appropriate responses internally.

VOCAB:

• Signal Transduction: The process in which an external signal leads to an intracellular change in behavior, enabling the cell to react to its environment.

• Gene Expression: The regulation of the types and quantities of genes that are activated (turned on) or silenced (turned off) within a cell, influencing the cell's function and development.

• Gene: A distinct sequence of DNA that encodes for a specific protein, which in turn performs a specific function within the cell or organism.

• Receptor: A specialized protein located on the cell surface that interacts with specific signaling molecules (ligands), initiating a cellular response.

• Ligand: An external signaling molecule that binds specifically to a receptor, triggering a signal transduction pathway.

• Relay Proteins: Proteins that facilitate the transfer of signaling information within the cell, acting as intermediaries in a signaling cascade to propagate the signal.

• Second Messenger: Small intracellular signaling molecules released as a consequence of receptor-ligand interactions, amplifying the signal within the cell.

• Transcription Factor: A protein that governs the rate of transcription of genetic information from DNA to messenger RNA, thereby regulating gene expression. Under specific conditions, a transcription factor can either enhance or inhibit gene expression.

• Signaling Cascade: A series of biochemical events inside the cell initiated by a receptor binding to a ligand. This cascade often involves relay proteins and second messengers and typically culminates in modifications to gene expression through the activation or deactivation

Steps of Signal Transduction

(Main points are Reception, Transduction, and then Response)

Protein Kinases are very common relay proteins - these are proteins that break down ATP and add the phosphate to a protein, thereby activating it(or inactivating it)

Many signal transduction pathways are carried out by relay proteins - proteins that interact with other proteins to either activate or deactivate them.

Some signal transduction pathways use relay proteins for activation, but some also use second messengers. These are small molecules that are either transported into the cell or released by intracellular mechanisms.

These then bind to other proteins to activate them, leading to a cellular response. They play roles in signal transduction very similarly to relay proteins, but they are not the same.

1. Ligand Binding: The process begins when a signaling molecule (ligand) binds to a specific receptor on the cell surface.

2. Receptor Activation: The binding induces a conformational change in the receptor, activating it and initiating the signal transduction pathway.

3. Relay Proteins Activation: Activated receptors interact with relay proteins inside the cell, which propagate the signal further.

4. Second Messenger Production: The interaction may trigger the production of second messengers (e.g., cAMP, calcium ions) that amplify the signal within the cell.

5. Signaling Cascade: This leads to a series of biochemical events (signaling cascade), often involving multiple proteins that further transfer and process the signal.

6. Transcription Factor Activation: Ultimately, the cascade may activate transcription factors that enter the nucleus to regulate gene expression.

7. Cellular Response: The final outcome involves various cellular responses such as changes in gene expression, cellular metabolism, or alterations in cell behavior.

Changing the Signal Transduction Pathway

Changes in signal transduction pathways can significantly influence cellular responses to various stimuli, affecting the overall function and health of the organism.Modifications or alterations in specific domains of receptor proteins or in the components of the signaling pathways may lead to profound changes in the cellular response, including the increase or decrease of gene expression, metabolic activity, or cell survival. These alterations can disrupt the normal flow of signal transduction by impacting receptor activation, signal propagation, or the final cellular outcome. For example, changes in receptor structure might affect ligand binding affinity or the receptor's ability to activate specific relay proteins. Consequently, this can lead to cell dysfunction or inappropriate cellular responses in various physiological contexts.

Examples

• DNA Changes: Mutations in the DNA sequence can alter the coding region of genes that produce proteins integral to signaling pathways, resulting in changes in amino acid sequences. These changes can affect protein stability, functionality, or interaction with other cellular components, leading to altered signaling outcomes.

• Poisons/Toxins: Certain environmental toxins or poisons may bind to proteins inappropriately, leading to their activation or inactivation. For example, neurotoxins can interfere with neurotransmitter signaling by preventing ligand binding or enhancing receptor activation beyond regulated levels, causing severe physiological consequences

Feedback Mechanisms

• Hormones are a signaling molecule produced by one tissue or organ of the body which travels through the bloodstream to cause some response in a different organ or tissue.

Feedback mechanisms, in general, are systems that respond to a disruption. In the endocrine system, feedback mechanisms allow an organism to regulate the secretion of, or response to, hormones, allowing the organism to maintain homeostasis.

Negative Feedback

Example: When you drink a large amount of water, your body desires to continue homeostasis. This process is triggered by endocrine hormones that regulate the kidneys to retain a proper balance of blood to water levels within the body.

Positive Feedback

Positive feedback is a regulatory mechanism in biology where the response to a stimulus increases the effect of that stimulus. Unlike negative feedback, which stabilizes a system by reducing the effects of a stimulus, positive feedback amplifies responses, leading to a greater change in the same direction. This process is crucial in various biological systems, particularly in events such as childbirth and blood clotting.

Example: Childbirth

During childbirth, the release of the hormone oxytocin triggers contractions in the uterus. As contractions occur, they push the baby toward the birth canal, which stimulates further release of oxytocin. This cycle continues, with each contraction leading to more oxytocin release until the baby is delivered. This exemplifies how positive feedback mechanisms can drive significant physiological changes.

Example: Blood Clotting

In the case of blood clotting, platelets adhere to a site of injury and release chemicals that attract more platelets. This accumulation continues to amplify the clot formation until the bleeding stops, showcasing the importance of positive feedback in maintaining homeostasis during injuries.

In conclusion, positive feedback loops play a critical role in many large-scale biological processes, facilitating rapid changes necessary for specific outcomes, such as childbirth and injury response, by enhancing the original stimulus.

Cell Cycle and Mitosis

Organisms must be able to create more cells to gain mass and sustain their growth. The process of cell division plays a critical role in this, enabling the reproduction of cells from preexisting ones. This cell cycle is not only about growth but also involves crucial processes of cell replenishment and repair, allowing organisms to recreate and replace dead or damaged cells whenever necessary. For instance, in human tissues, cells in the skin and blood must continuously divide to replace old or injured cells, ensuring the maintenance of optimal function.

Cells can reproduce through different mechanisms, one of which is asexual reproduction, commonly occurring in single-celled organisms like bacteria. In asexual reproduction, a cell divides to form two genetically identical daughter cells, allowing for rapid population growth under favorable conditions. This mechanism contrasts with sexual reproduction, where genetic material from two parent cells is combined, resulting in genetic diversity.

The cell cycle is divided into specific phases:

1. G1 (Gap 1): During this phase, the cell experiences growth, synthesizes proteins, and produces organelles. It also carries out its normal metabolic functions and assesses environmental conditions to determine if it should proceed with division.

2. S Phase: DNA replication occurs in this phase, doubling the genetic material in preparation for mitosis.

3. G2 (Gap 2): Following DNA synthesis, the cell continues to grow and makes final preparations for division. This includes the production of additional proteins and organelles, while also checking for any DNA replication errors to ensure genomic integrity.

4. Mitosis: This process involves the careful organization and separation of duplicated chromosomes, resulting in two identical daughter cells. It can be further broken down into distinct stages: prophase, metaphase, anaphase, and telophase, which collectively ensure the accurate distribution of genetic material.

Interphase

Interphase: Interphase is the longest phase of the cell cycle and encompasses the periods when the cell is not actively dividing. It is divided into three stages: G1 (Gap 1), S (Synthesis), and G2 (Gap 2).

• G1 Phase: The cell grows, synthesizes proteins, and produces organelles while carrying out its normal metabolic functions. During this phase, it assesses environmental conditions to determine if it should proceed with division.

• S Phase: This phase is characterized by DNA replication, where the cell duplicates its genetic material in preparation for mitosis. Each chromosome is copied to ensure that each daughter cell will receive the full set of chromosomes.

• G2 Phase: Following DNA synthesis, the cell continues to grow and makes final preparations for cell division. This includes producing additional proteins and organelles, as well as checking for any replication errors to ensure genomic integrity before mitosis begins.

Process(In Depth)

• Prophase is the first stage of mitosis where chromatin condenses into visible chromosomes, each with two sister chromatids joined at the centromere. The nuclear envelope disintegrates, allowing spindle fibers to access chromosomes, while the mitotic spindle forms from microtubules extending from centrosomes at opposite poles of the cell. The nucleolus disappears, and kinetochores form at the centromeres, crucial for chromosome movement. These processes ensure proper genetic distribution and maintain genomic integrity during cell division.

• Metaphase:

  • The second stage of mitosis where chromosomes align at the cell's equatorial plane (metaphase plate).

  • Each chromosome is attached to spindle fibers at its kinetochores, which are located at the centromere.

  • The alignment of chromosomes ensures that each daughter cell will receive an identical set of chromosomes during cell division.

  • The spindle checkpoint occurs during this phase to ensure all chromosomes are properly attached

• Anaphase:

  • The third stage of mitosis that follows metaphase.

  • During anaphase, sister chromatids are pulled apart at the centromere and move toward opposite poles of the cell.

  • The centromeres split, ensuring each daughter cell receives an identical set of chromosomes.

  • This movement is facilitated by the spindle apparatus, which contracts and helps separate the chromatids.

  • Anaphase ensures the accurate distribution of genetic material, crucial for maintaining genomic integrity during cell division.

Telophase:

• Telophase is the final stage of mitosis that begins once the sister chromatids have been pulled apart and moved to opposite poles of the cell during anaphase.

• During telophase, the chromosomes, which were previously condensed, begin to de-condense back into chromatin, making them less visible under a microscope.

• A nuclear envelope reforms around each set of chromosomes at the poles, resulting in two distinct nuclei within the cell.

• This phase also involves the reappearance of the nucleolus within the newly formed nuclei.

• Telophase marks the near completion of mitosis, leading to the final separation of the cytoplasm

Cell Cycle Regulation

REVIEW: The cell cycle has several checkpoints to decide if going through the cell cycle is the proper thing to do. Regulation is carried out through both physical and chemical signaling.

The three checkpoints are: The G1 Checkpoint, G2 checkpoint, and metaphase/spindle checkpoint.

Each checkpoint ensures that different conditions are true so that the cell cycle can proceed. If the conditions are not met, the cell will either exit the cell cycle, enter the G0 phase, or kill itself.

G1 Checkpoint: Occurs at the end of the G1 Phase…The checkpoint is a stopping place where it checks for:

• Available Nutrients

• -DNA Damage

• -Growth Factors (Chemical signaling that promotes cell cycle progression)

Why should/would a cell stop at the G1 checkpoint?

• No cells to replace

• No room to grow

• DNA is damaged or broken and the cell should commit suicide(apoptosis) - controlled cell death

• Not enough available nutrients to sustain new cells

G2 Checkpoint: Occurring at the end of the G2 phase. The G2 Checkpoint checks for:

• DNA Replication Completion

• Cell Size

-Cell must have two complete sets of DNA, one for each daughter cell to be produced. If not, must finish DNA replication first.

Metaphase Checkpoint: Spindle fibers have attached to chromosomes at the centromere. Replicated chromosomes are aligned at the metaphase plate.

If the metaphase checkpoint fails, the daughter cells produced by mitosis might not have the correct amount of chromosomes.

Too many or too few chromosomes always causes problems and can even be lethal.

Proteins that control the cell cycle’s regulation are Cyclins Kinases.

Proto-oncogenes: Genes that promote cellular division

Tumor Suppressor Genes: Genes that inhibit cellular division