Week 7 Cell communication Flashcards

1
Q

Signal transduction pathways

A

convert extracellular signals into cellular responses

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2
Q

2 types of cell communication:

A
  1. Local signaling: neighbouring cells communicate though cell junctions, cell-to-cell recognition or local regulators
  2. Long distance signaling: distant cells in multicellular organisms communicate using chemical messengers (e.g. hormones)
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3
Q

In local signaling, cells may communicate by (3):

A

Direct contact: via cell junctions (animal and plant cells); directly connect the cytoplasm of adjacent cells => coordinate the function of neighbouring cells in a tissue

Cell-cell recognition: via surface molecules (animal cells only); communicate and recognize each other via direct contact using surface molecules (e.g. membrane carbohydrates)

Local regulators: in paracrine/synaptic signaling (animal cells only) - messenger molecules that travel only short distances (e.g. growth factors, neurotransmitters)

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4
Q

Local signaling: communication by local regulators mechanisms described:

A

Paracrine signaling: A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.

Synaptic signaling: A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. (Electrical signal along nerve cell triggers release of neurotransmitter => Neurotransmitter diffuses across synapse => Target cell is stimulated)

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5
Q

Cell junction types: cell-to-cell connection

Communicating junctions (2):

A
  • Gap junctions: in animal cells, no cytoskeletal connection
  • Plasmodesmata: in plant cells, no cytoskeletal connection

Connect cytoplasm of neighboring cells directly

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6
Q

Cell junction types: cell-to-cell connection

Occluding junctions (1):

A

Tight junctions: connect with actin microfilaments

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7
Q

Cell junction types: cell-to-cell connection

Anchoring junctions (2) and connect w/:

A
  • Desmosomes: connect with intermediate filaments
  • Adherens junctions: connect with actin microfilaments
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8
Q

Gap junctions: communicating junctions (structure, exchange - ?, function, location, examples)

A

Structure: Cytoplasmic channels made by membrane proteins (connexins) connecting adjacent cells; necessary for cell-to-cell communication

Exchange: small molecule and ion exchange b/w cells (e.g. cAMP, Ca+2)

Function: Cell communication

Location: Located along the apical surfaces of cells of various tissues (e.g. epithelial cells and heart muscle)

Examples: Transport of Ca+2 b/w neighbouring smooth muscle cells through gap junctions => Synchronized contraction of intestine and uterus during birth

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9
Q

Tight junctions: communicating junctions (structure, exchange - ?, function, location)

A

Structure: Made by 2 types of transmembrane proteins - claudin and occludin; the cytoplasmic part of occludin is linked to the actin microfilaments

Exchange: NO. Create an exclusion zone around the cells => prevent leakage of extracellular fluid from a layer of epithelial cells (e.g skin layer)

Function: Inhibit cell-to-cell communication (molecule exchange)

Location: Underneath the apical surface of epithelial cells

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10
Q

Anchoring junction types (2 groups with 2 types in each):

A

• Connect neighbouring cells (Cell-to-cell connection):
- Desmosomes
- Adherens junctions

• Connect cells with ECM (Cell to ECM connection):
- Focal adhesions
- Hemidesmosomes

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11
Q

Desmosomes (function, cytoskeletal connection, intercellular connection, clinical correlation)

A
  • Fn: fasten cells together into strong sheets
  • Anchor to the cytoplasm through intermediate filaments (e.g. keratin in epithelial cells, desmin in heart muscle cells & smooth muscle cells)
  • Connect cells via transmembrane adhesion proteins (cadherins)
  • Clinical correlation. Desmosomes attach muscle cells to each other in a muscle => Some ‘muscle tears’ involve the rupture of desmosomes
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12
Q

Desmosomes: structure picture

A

transmembrane adhesion protein (cadherin) in extracellular space connects to intermediate filaments inside the cell through an attachment protein

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13
Q

Adherens junctions (fn, cytoskeletal connection, intercellular connection)

A
  • Fn: create adhesion zone (belt) underneath the apical surface of epithelial cells
  • Intracellular attachment proteins (catenins, vinculin, α-actinin): connect cadherins with actin microfilaments
  • Connect the plasma membranes of neighbouring cells via transmembrane adhesion proteins (cadherins)
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14
Q

Adherens junctions vs desmosomes

A

Similar except for cytoskeletal connection (Actin microfilaments for Adherence junctions and Intermediate filaments for Desmosomes)

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15
Q

Focal adhesions / Focal contacts (cytoskeletal connection, ECM (extracellular) connection):

A
  • Intracellular connection: Integrin cytoplasmic domain connects with actin microfilaments through attachment proteins (talin, α-actinin, vincoulin)
  • Extracellular connection: Connect cells to the ECM through integrins (transmembrane proteins), which bind to glycoprotein in ECM
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16
Q

Hemidesmosomes (cytoskeletal connection, ECM (extracellular) connection, location):

A
  • Intracellular connection: connect with keratin intermediate filaments through attachment proteins (plectin)
  • Extracellular connection: Stabilise epithelial cells by anchoring them to the ECM through integrins (transmembrane proteins; integrin binds to basement membrane laminin)
  • Found mainly in basal surface of epithelial cells
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17
Q

Anchoring junctions summary: Desmosomes (cell-cell)

Transmembrane linker protein -
Extracellular ligand -
Intracellular Cytoskeletal Attachment -

A

Transmembrane linker protein - cadherin (desmogleins & desmocollins)
Extracellular ligand - cadherin in neighboring cell
Intracellular Cytoskeletal Attachment - intermediate filaments

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18
Q

Anchoring junctions summary: Adherens junctions (cell-cell)

Transmembrane linker protein -
Extracellular ligand -
Intracellular Cytoskeletal Attachment -

A

Transmembrane linker protein - cadherin (E-cadherin)
Extracellular ligand - cadherin in neighboring cell
Intracellular Cytoskeletal Attachment - actin filaments

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19
Q

Anchoring junctions summary: Focal adhesions (cell-EM)

Transmembrane linker protein -
Extracellular ligand -
Intracellular Cytoskeletal Attachment -

A

Transmembrane linker protein - integrin
Extracellular ligand - EM proteins
Intracellular Cytoskeletal Attachment - actin filaments

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20
Q

Anchoring junctions summary: Hemidesmosomes (cell-EM)

Transmembrane linker protein -
Extracellular ligand -
Intracellular Cytoskeletal Attachment -

A

Transmembrane linker protein - integrin (α6,β4)
Extracellular ligand - basal lamina proteins
Intracellular Cytoskeletal Attachment - intermediate filaments

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21
Q

Summary of animal cell junctions: functions

Tight junction:

A

seals neighboring cells together in an epithelial sheet to prevent leakage of molecules b/w them

22
Q

Summary of animal cell junctions: functions

Adherens junction:

A

joins an actin bundle in one cell to a similar bundle in a neighboring cell

23
Q

Summary of animal cell junctions: functions

Desmosome

A

joins the intermediate filaments in one cell to those in a neighboring cell

24
Q

Summary of animal cell junctions: functions

Gap junction

A

allows passage of small water-soluble ions and molecules

25
Q

Summary of animal cell junctions: functions

Hemidesmosome

A

anchors intermediate filaments in a cell to the basal lamina

26
Q

Summary of animal cell junctions: functions

Focal adhesions:

A

Anchors actin microfilaments to the basal lamina (ECM type)

27
Q

The Three Stages of Cell Signaling

A
  1. Reception
  2. Transduction
  3. Response
28
Q

Reception -

A

the signaling molecule (ligand) binds to a receptor protein, causing conformational change, which then initiates the process of transduction

29
Q

conformational change -

A

change of shape of a receptor protein due to ligand binding

30
Q

Receptor types (2):

A
  • Plasma membrane receptors (majority)
  • Intracellular receptors (minority)
31
Q

Intracellular receptors - 2 types and what signaling molecules use them?

Examples

Clinical correlation

A
  1. cytoplasmic proteins
  2. nuclear proteins

Signaling molecules that are small or hydrophobic and can readily cross the plasma membrane use these receptors

Ex: steroid hormones: estrogens (e.g. estradiol) and androgens (e.g. testosterone) bind to intracellular steroid receptors: Estrogen receptors (ERs) and androgen receptors (ARs)

Clinical correlation: tamoxifen - drug used for treatment of ER+ breast cancer (ER+: expresses the estrogen receptors like normal tissue which is better prognosis than ER- b/c the latter is less differentiated, loss its expression, more invasive)
Mode of action of tamoxifen: Estrogen antagonist (binds to the ER and prevents estradiol binding)

32
Q

three main types of plasma membrane receptors:

A

– G-protein-coupled
– Tyrosine kinases
– Ion channels

33
Q

G protein-coupled receptors -

A

plasma membrane receptors linked to a G protein

34
Q

G-proteins - what are they and clinical correlation (2)

A

proteins bound to GTP/GDP, act as an on/off switch:
– If GDP is bound to the G protein => G protein is inactive
– If GTP is bound to the G protein => G protein is active
=> hydrolysis can inactivate them

Clinical correlation:
1. Involved in many human diseases, including bacterial infections: cholera toxin and botulinum toxin are bacterial products that interfere with G protein function
2. More than 60% of all medicines used today exert their effects by influencing G protein pathways

35
Q

Protein kinases -

A

enzymes that phosphorylates protein substrates (add phosphate groups to them)

36
Q

Receptor tyrosine kinases: definition, structure, examples, mode of action

A

transmembrane receptors that attach phosphates to tyrosine residues

3 domains: Extracellular ligand binding domain, Transmembrane domain, Intracellular domain with tyrosine kinase activity

Ex: Growth factor receptors are commonly receptor tyrosine kinases (e.g. EGFR (epidermal growth factor receptor), PDGFR (platelet derived growth factor receptor))

Growth factor binding to their receptor tyrosine kinases => Activation of signal transduction pathways such as the MAPK pathway (MAPK - Mitogen Activated Protein Kinase) => DNA polymerase production for further cell division

37
Q

Receptor tyrosine kinases scheme:

A

Ligand binding => receptor dimerization => Autophosphorylation of tyrosine residues => activation => Phosphorylation of other proteins => Activation of signal transduction pathways (e.g. MAPK pathway)

38
Q

Receptor tyrosine kinases: clinical correlations

A

Abnormal tyrosine kinase receptors may contribute to some kinds of cancer: truncated receptors that function in the absence of signaling molecules (lack the ligand-binding domain) => overexpression/ amplification of receptors => overproduction of protein.

Ex: EGFR (Epidermal Growth Factor Receptor) amplification (overexpression) in many cancers (e.g. breast cancer - HER2+)

Several anti-cancer drugs block tyrosine kinase activity:
herceptin - monoclonal antibody that competes w/ EGF in EGFR
Gleevec - blocks enzymatic activity of the receptor => it can’t go into phosphorylation => activation of transduction is blocked

39
Q

Transduction -

A

signal from the receptor converted to a form that can cause a specific cellular response, usually requires a series of changes in a series of different target molecules

40
Q

Signal transduction pathways -

A

cascades of molecular interactions that relay signals from receptors to target molecules in the cell; at each step in a pathway the signal is transduced into a different form (usually a conformational change in a protein)

41
Q

Protein Phosphorylation and Dephosphorylation: participants of the process

A

Protein kinases: enzymes that add a phosphate to the next protein kinase in line => activate protein kinases
Phosphatases: enzymes that remove the phosphates => deactivate the protein kinases

42
Q

Second messengers -

A

small, non-protein, water-soluble molecules or ions that act in the signal transduction pathways (after the action of first messenger - ligand)

cAMP, Ca+2, IP3, DAG

43
Q

Cyclic AMP (cAMP):

A

Produced from ATP through the enzyme adenylyl cyclase which takes out 2 phosphate groups

Many G-proteins trigger the formation of cAMP, it then acts as a second messenger in the signal
transduction pathways

44
Q

Inositol Triphosphate (IP3) and Diacylglycerol (DAG):

A

IP3 triggers an increase in Ca2+ concentration in the cytosol

Activated G protein activates phospholipase C => Phospholipase C cleaves a plasma membrane phospholipid called PIP2 (twice phosphorylated phosphatidilinositol) into DAG and IP3 => DAG causes variety of cell responses, IP3 goes to IP3-gated Ca2+ channels in smooth ER => Ca2+ goes into cytosol (facilitated diffusion)

45
Q

Response (2 types) -

A

transduced signal triggers a specific cellular response: regulation of cytoplasmic activities
(cytoplasmic response) or transcription (nuclear response)

46
Q

Example of Cytoplasmic response to a signal -

A

Glycogen breakdown into glucose

47
Q

Example of Nuclear response to a signal -

A

steroid hormone signaling pathways, MAPK signaling cascade

48
Q

Basement membrane (basal lamina) -

A

specialized ECM type that separates an endothelial cell layer form the underlying connective tissue

49
Q

Connective tissue -

A

consists mostly of ECM secreted by the fibroblasts

50
Q

Cyclic AMP signal transduction pathway:

A

Many G-proteins trigger formation of cAMP => cAMP acts as a second messenger in the signal transduction pathways

First messenger (ex: epinephrine) binds to G-protein- linked receptor + GTP => Adenylyl cyclase => ATP - cAMP (second messenger) => Protein kinase A =»> cellular responses