20. Cell Signaling 1 – Overview

MIT OpenCourseWare

12 May 202048:34

EducationalLearning

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TLDRThe video discusses protein cellular signaling, a complex communication system that governs cell activities. It outlines the three basic steps of signal transduction - receiving a signal, transducing it, and generating a response. It then examines key features like signal specificity, amplification cascades, feedback loops, and pathway integration. The video looks at signal types - autocrine, paracrine, juxtacrine, endocrine - and receptor types like G protein-coupled receptors and receptor tyrosine kinases that bind signals at the cell surface to trigger intracellular signaling events.

Takeaways

😀 Proteins are defined by DNA sequence, which impacts folding, misfolding, localization and more
👩‍🔬 Misfolded proteins can aggregate, causing diseases like Alzheimer's and mad cow disease
💡 Signaling is communication governing cell activities through receptors, transduction and responses
🔍 Specificity, amplification, feedback and integration characterize signaling pathways
📝 Signals can be small molecules or proteins, named for origin - autocrine, paracrine, etc.
🔬 Steroids can cross membrane and bind intracellular receptors, altering transcription
🚪 GPCRs, receptor tyrosine kinases and ion channels are key plasma membrane signaling proteins
👍🏻 GPCRs have 7 membrane-spanning helices, bind extracellular signals to cause intracellular changes
⚛️ Binding a GPCR clamps the protein, transducing outside-to-inside signal
🧬 Signaling pathways control critical cell activities like division, ATP production and more

Q & A

What are the three basic steps of protein signaling?
-The three basic steps of protein signaling are: 1) Receive a signal, 2) Transduce the signal, and 3) Generate a response.
What is a chaperone protein and what does it do?
-A chaperone protein helps other proteins fold properly and prevents misfolding. It holds onto partially folded proteins until they can adopt a favorable folded state.
What is the proteasome and what is its function?
-The proteasome is like a cellular shredder or protease that breaks down misfolded proteins into small peptides. It helps the cell dispose of aggregated or damaged proteins.
What are prion diseases and how are they caused?
-Prion diseases are neurological disorders like mad cow disease that are caused by misfolded proteins. The misfolded prion proteins can nucleate and generate more misfolded proteins, resulting in disease.
What are the four types of signaling between cells?
-The four types are: 1) Autocrine - cell signals itself, 2) Paracrine - cell signals nearby cells, 3) Juxtacrine - signaling between contacting cells, and 4) Endocrine - signaling from distant cells.
What are the key classes of cell surface receptors?
-The key classes are: 1) G protein-coupled receptors, 2) Receptor tyrosine kinases, and 3) Ion channels.
How do steroid hormones like cortisol signal inside cells?
-Steroid hormones are hydrophobic so they can pass through the cell membrane without a transporter and bind to intracellular receptors.
What is a cascade in signaling?
-A signaling cascade is an amplifying series of molecular events, where one activated molecule triggers activation of many more molecules in sequence.
What is negative feedback in signaling?
-Negative feedback is where a downstream product inhibits an upstream step in a pathway. This turns the pathway off once it has been sufficiently activated.
What is integration in complex signaling networks?
-Integration refers to crosstalk between pathways, where multiple signals modulate and balance each other's activities for an overall coordinated cellular response.

Outlines

00:00

🧬 Defining Protein Sequences and Misfolding from DNA

Paragraph 1 discusses how protein sequences, folding, and misfolding are ultimately defined by DNA. It explains that while there may be some regulation at other levels, DNA provides the original sequence that dictates protein structure and function. Misfolded proteins can cause aggregation and disease.

05:00

😷 Cellular Systems for Dealing with Misfolded Proteins

Paragraph 2 describes cellular systems for dealing with misfolded proteins. Chaperone proteins can help with protein folding by protecting hydrophobic regions. Ubiquitination tags misfolded proteins for destruction by the proteasome, which chops proteins into small peptides that won't aggregate.

10:01

🧠 Diseases Caused by Protein Misfolding

Paragraph 3 discusses diseases caused by protein misfolding such as mad cow disease, Alzheimer's, and other neurological disorders. These prion diseases involve intercellular transmission of misfolded proteins that propagate aggregation.

15:02

👪 Inherited Protein Misfolding Diseases

Paragraph 4 notes that some protein misfolding diseases like Alzheimer's have genetic links. Mutations can make proteins prone to misfolding, showing how DNA errors translate into pathogenic protein conformations.

20:05

🔄 The Basics of Cellular Signaling Pathways

Paragraph 5 introduces cellular signaling as a complex communication system governing cell activities through receptors, signal transduction, and responses. It outlines simple signaling steps and notes integration of pathways.

25:08

🗺️ Mapping Complex Signaling Networks

Paragraph 6 describes systems biology approaches to map signaling networks, tracing signaling proteins and interactions through experiments, computations, and modeling flux.

30:10

🔑 Key Features of Signal Transduction

Paragraph 7 outlines key characteristics of signal transduction: specificity of signals for receptors, amplification into cascades, feedback regulation, and integration of multiple pathways.

35:10

📟 Monitoring Live Juxtacrine Signaling

Paragraph 8 shows a video of juxtacrine signaling, where calcium fluxes propagate between contacting cells.

40:12

👂 Types of Signaling by Source and Reception

Paragraph 9 defines terms for signals based on their source (autocrine, paracrine, endocrine, juxtacrine). Most bind surface receptors, some intracellular.

45:12

📱 Major Classes of Cell Surface Receptors

Paragraph 10 introduces three receptor types: G protein-coupled, receptor tyrosine kinases, and ion channels. Notes their drug targeting and structural features for signaling.

Mindmap

Keywords

💡Cellular signaling

Cellular signaling is a complex communication system that governs all basic cell activities. It involves receiving signals, transducing them within the cell, and generating a response. Signals may come from outside or inside the cell and involve binding to specific receptors.

💡Signal specificity

A key aspect of signaling is that signals bind to specific receptors. Signals like hormones must bind only to their matched receptors and not to other similar receptors, even at low concentrations. This specificity comes from the highly specific macromolecular interactions between the signal and receptor.

💡Signal amplification

An important feature of signaling is amplification of the signal, where binding of one or a few signal molecules leads to a much larger cellular response. This often happens through enzyme cascades, where each enzyme activates many more copies of the next enzyme.

💡Autocrine signaling

One way signals are classified is by their origin. Autocrine signals come from the same cell they are signaling to. An example is a cell releasing a factor that then binds to and signals that same cell.

💡Steroid receptors

Steroid hormones like cortisol can cross the cell membrane and bind to intracellular receptors, since they are hydrophobic. This causes conformational changes in the receptor that allow it to move to the nucleus and alter gene transcription.

💡GPCRs

G protein-coupled receptors (GPCRs) are an important class of cell surface receptors with 7 membrane-spanning helices. Many drugs target GPCRs. Binding of ligands to the extracellular side causes changes on the intracellular side.

💡Receptor tyrosine kinases

Another key signaling receptor class is the receptor tyrosine kinases, which are dimeric proteins. Ligand binding causes them to dimerize, leading to signaling cascades inside the cell, often involving phosphorylation.

💡Ion channels

Ion channels are proteins that span the membrane and open to allow ions to flow in/out of the cell. They act as receptors by changing confirmation in response to signals, leading to rapid electrical changes.

💡Feedback

Signaling pathways involve feedback loops to shut off signaling after the appropriate response. This is often negative feedback where a signaling product inhibits its own pathway.

💡Crosstalk

Signaling systems have extensive crosstalk and integration between pathways. One pathway may amplify or inhibit another through shared components, allowing complex signaling integration.

Highlights

Protein signaling is a complex communication system that governs all basic cell activities

Protein signaling can be divided into 3 steps - receive a signal, transduce the signal, and generate a response

Cell surface receptors like receptor tyrosine kinases and G protein-coupled receptors are critical for signaling

Signals can be classified as autocrine (self), paracrine (nearby cells), juxtacrine (contacting cells) or endocrine (distant)

Steroids can cross the membrane and bind to intracellular receptors to initiate signaling

Key features of signaling include specificity, amplification, feedback and integration

Misfolded proteins can aggregate and cause diseases like mad cow disease and Alzheimer's

The ubiqutin system tags misfolded proteins for degradation by the proteasome

Chaperone proteins help proteins fold properly and prevent aggregation

Signaling networks allow crosstalk between pathways to modulate responses

Systems biology models signaling networks and pathways in cells

Amplification rapidly increases the signal through enzyme cascades

Negative feedback loops help turn off signaling pathways

High specificity binding allows response at low signal concentrations

DNA sequence ultimately defines protein folding and function

Transcripts

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