Topic 7: cell communication Flashcards
Define signal transduction pathways
Convert extracellular signals into cellular responses
2 types of cell communication
1) Local signaling: neighboring cells communicate
2) Long-distance signaling: distant cells in multicellular organisms communicate via chemical messengers
Types of local signaling
1) Direct contact: cell junctions
2) Cell-cell recognition: surface molecules
3) Local regulators: synaptic signaling
Describe direct contact
- Both plants/animals have cell junctions directly connecting cytoplasm of adjacent cells
- Coordinate function of neighboring cells in a tissue
Describe cell-cell recognition
- Animal cells recognize each other via direct contact using membrane carbohydrates/receptors
Describe local regulators
- Messenger molecules travel short distances
- E.g. growth factors + neurotransmitters
- Paracrine = secreting cell acts on target cell
- Synaptic = nerve cell into synapse onto target cell
Cell junction types
COMMUNICATING JUNCTIONS:
- Gap junctions = animals + no cytoskeletal connection
- Plasmodesmata = plants + no cytoskeletal connection
OCCLUDING JUNCTIONS:
- Tight junctions = connect with actin filaments
ANCHORING JUNCTIONS:
- Desmosomes = connect with intermediate filaments
- Adherens junctions = connect with actin microfilaments
Describe plasmodesmatas
- Channels connecting neighboring cells
- Allow cell communication + molecule exchange of small molecules/water
Describe gap junctions
- Cytoplasmic channel = connect adjacent cells
- Made of membrane protein = connexin
- Allow exchange of small molecules + ion exchange e.g. cAMP + Ca2+
- Located = apical surface of cells e.g. epithelial + heart muscle
- Transport Ca2+ between neighboring smooth muscle cells = allows synchronized contraction of intestine + uterus during birth
Describe tight junctions
- Located = underneath apical surface of epithelial cells
- Inhibit cell-cell communication + exchange
- Prevent leakage of extracellular fluid from epithelial cells
- Made by transmembrane proteins = claudin + occludin
- Cytoplasmic part of occludin linked to actin filaments
Types of anchoring junctions
CELL-CELL CONNECTION:
- Desmosomes = intermediate
- Adherens = actin
CELL - ECM CONNECTION:
- Focal adhesion = actin
- Hemidesmosomes = intermediate
Describe desmosomes
- Fasten cells together = strong sheets
- Anchor to cytoplasm via intermediate filaments e.g. keratin in epithelial + desmin in heart/smooth muscle cells
- Connect cells via transmembrane adhesion proteins = cadherins
- Attach muscle cells to each other = muscle tears are ruptured desmosomes
Describe adherens junctions
- Located = create adhesion zone under apical surface of epithelial cells
- Connect plasma membranes of neighboring cells via transmembrane proteins = cadherins
- Intercellular attachment proteins = connect cadherins + actin microfilaments
Describe focal adhesions
- Extracellular connection = connect cells to ECM via integrins
- Intracellular connection = integrin connects with actin via attachment proteins
Describe hemidesmosomes
- Located = basal surface of epithelial
- Extracellular connection: stabilize epithelial by anchoring to ECM via integrins to basement membrane laminins
- Intracellular connection: connect with keratin intermediate filaments through attachment proteins
Define basement membrane
Specialized ECM type = separates endothelial cell from underlying connective tissue
Define connective tissue
Consists of ECM secreted by fibroblasts
Define long-distance signaling
- In plants + animals
- Hormonal signaling AKA endocrine signaling
- Specialized cells release hormone = travels to target cell in body
3 stages of cell signaling
1) Reception
2) Transduction
3) Response
Explain reception
- Signaling molecule = ligand = binds to receptor protein = change shape
- Binding is highly specific
- Conformational change initiates process of transduction
2 Types of receptors
1) Plasma membrane receptors
2) Intracellular receptors
Describe intracellular receptors
- Cytoplasmic + nuclear proteins
- Used by signaling molecules that = small + hydrophobic + readily cross membrane
- E.g. steroid hormone + intracellular receptors = estrogen/androgen + ERs/ARs
What are the clinical correlations of intracellular receptors?
- Tamoxifen
- Drug used for ER+ breast cancer
- It is estrogen antagonist = binds to ER and prevents estradiol binding
Explain how steroid hormones act via intracellular receptors
1) Hormone passes through membrane
2) Binds to receptor protein in cytoplasm = activate
3) Hormone-receptor complex enters nucleus = bind to specific gene
4) Bound protein stimulates transcription of gene>mRNA
5) mRNA translated to specific protein
3 Types of plasma membrane receptors
- G-protein-coupled
- Tyrosine kinases
- Ion channels
Describe G-protein-coupled receptors
- Linked to G protein = bound to GTP/GDP
- G protein acts as on/off switch:
> GDP when bound = G protein inactive
> GTP when bound = G protein active
What is the involvement of G protein receptors in human disease?
- E.g. bacterial infections
- Cholera + botulinum toxin = bacterial products = interfere with G protein function
- > 60% meds exert effects by influencing G protein pathways
Describe receptor tyrosine kinases
- Protein kinases = enzymes that phosphorylate protein substrates
- These are transmembrane receptors that attach phosphates to tyrosine residues
1) Extracellular = ligand binding domain
2) Intracellular = tyrosine kinase activity - Growth factor receptors = tyrosine kinases receptors
- Growth factors bonding to receptor = activation of signal transduction pathways = MAPK
What is the clinical correlation of receptor tyrosine kinases?
- Abnormal TKR = contribute to cancer
- Receptors that function in absence of signaling molecules = lack ligand binding domain
- Overexpression of receptors = EGFR amplification in cancers e.g. breast cancer
- Anti-cancer drugs block tyrosine kinase activity e.g. Herceptin + Gleevac
Describe ion channel receptors
- Act as gates = open when receptor changes shape
1) Binding of signal molecule + receptor
2) Receptor changes shape = opens
3) Specific ions pass through channel
Explain transduction
- The signal from the receptor converted to form that can cause specific cellular response
- Requires signal transduction pathways = molecular interactions that relay signal from receptors > target
- Each step = signal transduced to different form = conformational change
Describe protein phosphorylation + dephosphorylation
- Some signal pathways = phosphorylation cascades
1) Protein kinases = enzyme add phospahte to next protein kinases in line = activate protein
2) Phosphatases = enzyme removes phosphates = deactivate protein
Define second messengers
- Small + non-protein + water-soluble molecules/ions = act in signal transduction pathways
- E.g. cAMP + Ca+2 + DAG + IP3
Describe cAMP
- Cyclic AMP = produced by ATP via enzyme adenylyl cyclase
- G proteins trigger the formation
- cAMP acts as second messenger in pathway
Describe calcium ions
- When released into cytosol = act as secondary messenger in many pathways
- Ca2+ = important messenger = cells able to regulate concentration cytosol
What is the function of IP3?
- Triggers an increase in Ca concentration in cytosol
Explain how second messengers work together
1) Signal molecule binds to receptor = activation of phospholipase C
2) Phospholipase C cleaves plasma membrane phospholipid PIP2 = DAG + 1P3
3) DAG = second messenger in other pathways
4) IP3 = diffuses through cytosol + binds to IP3 gated calcium channel = open
5) Ca2+ out of endoplasmic reticulum = Ca2+ increase in cytosol
6) Ca2+ activate next protein in 1 or more pathways
Explain response
- Transduced signal triggers specific cellular response
- Cell signaling = regulation of cytoplasmic activities + transcription
Describe the cytoplasmic response to a signal
- Signaling pathways regulate variety of cellular activities e.g. glycogen breakdown>glucose
1) Reception = binding of epinephrine to G-protein linked receptor
2) Transduction: - Inactive G protein > active
- Inactive adenylyl cyclase > active
- ATP > cAMP
- Inactive protein kinase A > active
3) Response = glycogen > glucose 1 phosphate
Describe the nuclear response to a signal
- Pathway regulates genes by activating transcription factors = turn gene expression on/off
- E.g. steroid hormones signaling pathway + MAPK signaling cascade
What are the benefits of multistep signaling pathways?
1) Amplification of signal= amplification of response
2) Contribution to specificity of response
- Therefore provides more opportunities for coordination + regulation
