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BIO109 > Topic 2: Cell-cell communication > Flashcards

Topic 2: Cell-cell communication Flashcards

1
Q

How do cells and tissues “know” how to develop?

A

Induction and competence

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2
Q

Proteins made by a cell or group of cells that alter the behavior and differentiation of adjacent cells
- inter and intracellular signals

A

Paracrine Factors

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3
Q

Response to signals at the molecular level

A

Signal transduction/ Signal transduction cascades

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4
Q

Proteins or signaling molecules, that exert their effects on neighboring cells by direct physical contact. This interaction triggers signaling pathways within the recipient cell, leading to changes in cell behavior, differentiation, or other cellular responses.

A

Juxtacrine siignaling/ Extracellular matrix signaling

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5
Q

Communication between cells requires:
1. The signaling molecule
2. The molecule to which the receptor binds
- may be on the plasma membrane or within the cell

A
  1. Ligand
  2. Receptor protein
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6
Q

Types of Cell Signaling:
1. The cell targets itself
2. A cell signals a nearby cell
3. A cell targets a distant cell through the bloodstream
4. A cell targets a neighboring cell through a gap junction

A

Autocrine signaling
Paracrine
Endocrine
Direct signaling / Juxtracrine

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7
Q

In Juxtacrine signaling (What type of binding):
1. Binding of an adhesion molecule in one cell to an identical molecule in an adjacent cell
2. Binding of an adhesion molecule in one cell to a non- identical adhesion molecule in an adjacent cell

A
  1. Homophilic binding
  2. Heterophilic binding
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8
Q

Types of Receptors

A

Internal receptors and Cell-surface receptors

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9
Q

Types of Receptors:
Found in the cytoplasm of target cells and respond to ___ ligand molecules that are able to travel across the plasma membrane.

A
  1. Internal receptors (intracellular or cytoplasmic receptors)

hydrophobic

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10
Q

Types of Receptors:
Are integral proteins that bind to external signaling molecules. These receptors span the plasma membrane and perform signal transduction, in which an extracellular signal is converted into an intercellular signal.

A

Cell-surface receptors (transmembrane receptors)

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11
Q

Receptor types: There are 3 subclasses of cell-surface receptors:
1. Ion channel that opens in response to a ligand
2. Receptor is an enzyme that activated by the ligand
3. A G-protein (bound to GTP) assists in transmitting the signal.

A
  1. Channel linked receptors
  2. Enzymatic receptors
  3. G protein- coupled receptor
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12
Q

3 stages of Signal Transduction
1. ___ of extracellular signal by cell
2. ___ of signal from outside of vell to inside of cell-often multi-stepped (note: not necessarily transduction of ligand)
3. Response is initiated and/or occurs entirely within receiving cell

A
  1. Reception
  2. Transduction
  3. Cellular Response
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13
Q

The interaction of the ligand and receptor protein. And it results in cellular response

A

Signal transduction

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14
Q

Interaction at close range between 2 or more cells or tissues with different histories and properties

A

Induction

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15
Q

The tissue that produces the signal that changes the cellular behavior of the other tissue

A

Inducer

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16
Q

The tissue being induced; the target tissue

A

Responder

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17
Q

Note- the target tissue must be capable of ____

A

Responding

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18
Q

The ability of a cell or tissue to respond to a specific inductive signal (Waddington 1940)

A

Competence

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19
Q

____ are outgrowings of the brain which make contact with the ____ and this contact induces changes necessary for further _____

A

Optic vesicles
Surface ectoderm
Development of the eye

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20
Q

____ (tissue thickening) induced in head ectoderm by close contact with neural (brain) tissue

The developing lens then induces brain to form the ___

A

Lens placode

Optic cup

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21
Q

The ability of a cell or tissue to respond to a specific inductive signal
- Actively acquired (and can also be translent)

A

Competence

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22
Q

It is a competence factor for lens induction

During lens induction ___is expressed in the head ectoderm, but not in other regions of surface ectoderm.

A

Pax6

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23
Q

In the recombination experiments using embryonic rat eye tissue, which is the defective component, the optic vesicle or the surface ectoderm?

___ is needed for the _____ to respond to the ___ from the optic vesicles; the inducing tissue does not need it.

A

Surface Ectoderm
- Pax6- deficient rats is caused by the inability of the surface ectoderm to respond to the optic vesicle.

Pax6; surface ectoderm;inductive signal

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24
Q

Refers to a signaling molecule or a group of molecules that initiates a specific developmental process or pathway in a target tissue or cell.

A

Inducer

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25
Q

The pigment layer and neural retina

Optic Vesicle (inducer) secrete signal to ___ and will differentiate to 2 ____

A

Optic cup

surface ectoderm; optic cup

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26
Q

Optic vesicle inducers

A

BMP4 (Bone morphogenic protein 40

Fgf8 (Fibroblast growth factor 8)

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27
Q

These induces:
BMP4 (Bone morphogenic protein 4)
Fgf8 (Fibroblast growth factor 8)

A

BMP4 induces Sox2 and Sox3 transcription factors

Fgf8 induces L-Maf transcription factor

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28
Q

Sequential and additive effects of multiple inducers for frog lens

A

1st inducer- pharyngeal endoderm and heart-forming mesoderm
2nd- inducer - anterior neural plate (including signal for ectoderm Pax6 synthesis)

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29
Q

The combination of Pax6, Sox2, Sox3 and L-Maf in the ectoderm ensures the production of the ___ and the activation of lens-specific genes such as ____

A

lens
crystallin

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30
Q

The optic cup will develop into

A

Retina - the pigmented retina and neural retina

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31
Q
  1. Under the influence of factrs secreted by the lens, the optic vesicle becomes the optic cup and the wall of the optic cup differentiates into 2 layers: the pigmented retine and neural retine. This interaction is called:
  2. A structure does not need to be fully differentiated in order to have a ___
  3. The optic vesicle induces before it becomes ____
  4. The ____ reciprocates by inducing the optic vesicle before the lens forms its characteristics fibers.
A

Reciprocal Induction:

function

retina

lens placode

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32
Q

How do these interactions work?

  1. A signal from the inducer is required for initiation new gene expression. Without the inducer, the cell is not capable of differentiating.
  2. The tissue has already been specified, but requires an environmental change that allows expression of the differentiated tissues traits.
A

Instructive Interaction

Permissive Interaction

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33
Q
  1. Sheets or tubes of connected cells
    - originate from any germ layer
  2. Loosely packed, unconnected cells
A

Epithelia

Mesenchyme (inducing tissue)

34
Q

All organs consist of an

A

Epithelium and an associated mesenchyme

35
Q

Epithelial- Mesenchymal Interactions
Example organ

A

Kidney
Tooth
Pharyngeal and respiratory associated organs
Gut organs
Limb
Cutaneous structures

36
Q

Source of the mesenchyme (inducing tissue) determines the structure of the epithelial derivative.

A

Regional Specificity

37
Q

Epithelial derivatives or ____:derivative type depends on restrictions by

A

Specific Induction

Region and Genetics

38
Q

A single organism that’s made up of cells from two or more individuals (2 sets of DNA)

A

Chimeras

39
Q

Epithelial response is limited to genomic capability

A

Genetic specificity

40
Q

Signaling molecules (proteins) produced by one cell (tissue) and distributed via diffusion to a localized area; often act as inducers.

A

Paracine Factors or Growth and Differentiation Factors (GDF)

41
Q

Paracrine factor families:

A
  1. FGF- Fibroblast Growth Factor
  2. Hedgehog family
  3. Wingless family (Wnt)
  4. TGF-B superfamily (Transforming growth factor)
    - TGF-B family
    - Activin family
    - Bone morphogenic proteins (BMP)
    - Vg1 family
42
Q

It is a common way to change the activity of a protein

A

Phosphorylation

43
Q

Phosphorylation:
1. An enzyme that adds a phosphate to a protein.
2. An enzyme that removes a phosphate from a protein.

A
  1. Protein kinase
  2. Phosphatase
44
Q

____ all appear to be variations on a common and rather elegant theme.
- are complex networks of molecular interactions that transmit signals from the extracellular environment to the interior of the cell, where they elicit specific cellular responses.

A

Signal Transduction Pathways

45
Q

The Different Signal Transduction Pathways

A

Paracrine Signaling Pathways:
1. RTK Pathway - Generic
2. JAK-STAT Pathway
3. Hedgehog Pathway- Generic
4. Wnt Pathways
- Intracellular Pathways: Wnt/b-catenin (canonical), Wnt/JNK, Wnt/ Calcium Dependent (Noncanonical Pathways)

Juxtacrine Signaling:
5. The Notch Pathway/ Notch Signaling Pathway

46
Q

RTK Pathway process summary

A
  1. Ligand Binding (a paracrine factor, fgf8)
  2. RTK
    - Dimerized/ Dimerization ( Mutapad ang duha ka monomer: both monomers change their conformation + dimer is formed;
    - RTK autophosphorylation ( one receptor is phorphorylating the other one.)
  3. GEF
    - Adaptor Protein Binding and activates an intermediate protein, GEF.
  4. RAS
    - GEF activates RAS G protein by allowing phosphorylation of the GDP- bound RAS.
    - At the same time, the GAP protein stimulates hydrolysis of this phosphate bond, returning RAS to its inactive state
  5. RAF
    - The active Ras activates Raf Protein Kinase C, which phosphorylates kinases such as MEK and ERK
  6. MEK
    - RAF activates MEK and other kinases
  7. ERK
    - the activated kinase ERK alters gene expression in the nucleus of the responding cell by phosphorylation certain transcription factors
  8. Transcription factor
    - phosphorylated transcription factor alters gene expression in the nucleus
  9. Transcription
    - In many cases, this pathway regulates the gene expression of ETS domain (E26 transformation- specific)
47
Q
  • Active during development
  • Repressed/silenced in adult
  • Cause tumor formation when inappropriately activated

Mutations (eg. consecutive activation)= ____

A

Proto-oncogenes

oncogene

oncogene

48
Q

The RTK pathway is critical in numerous developmental processes:
1. In the migrating neural crest cells of humans and mice, the pathwasy is important in activating the: ___

  1. Activate transcription of the genes encoding tyrosinease and other proteins of the melanin formation pathway
A
  1. Micropthaimia transcription factor (Mitf) to produce pigment cells (melanoblast cells, pigmented retina)
  2. p300/CBP histone acetyltransferase protein
49
Q
  1. A non-receptor tyrosine kinase
  2. A family transcription factor
A

JAK- Janus Kinase
STAT- Signal Transducers and Activators of Transcription

50
Q

JAK-STAT Pathway activators

A

Prolactin, Cytokines, growth hormones;

51
Q

JAK-STAT pathway is very important in the regulation of ___

Mutations that prematurely activate the STAT pathway have been implicated in some severe forms of ___ such as the lethal ____ (its short rib cannot support breath)

A

Human fetal bone growth

Dwarfism;

Thanatophoric dysplasia (Fibroblast growth factor Receptor 3 or FgfR3)

52
Q

JAK-STAT Pathway; Casein Gene activation process summary

A
  1. Ligand binding
    - Prolactin binds to Receptor
  2. Receptor
    - Prolactin causes the Dimerization of Prolactin receptor
  3. JAK
    - The JAK protein is ‘hitched” to the cytoplasmic domain of these receptors
    - the JAK proteins phosphorylates each other and the dimerized receptors , activating the dormant kinase.
  4. STAT
    - The activated receptors add a phosphate group to a tyosine residue of a STAT protein (Stat5)
  5. STAT dimerization
    - This addition allows Stat5 to dimerize, be translocated into the nucleus and bind bind to particular regions of DNA
  6. Transcription
    - In combination w other transcription factors, the Stat5 protein activates transcription of the casein gene.
53
Q

This pathway is extremely important in vertebrate limb and neural differentiation

A

The Hedgehog pathway

54
Q

One remarkable feature of Hedgehog signal transduction pathway is the importance of ___

A

Cholesterol

55
Q
  1. Cholesterol is critical for the catalytic cleavage of ___
  2. The cholesterol also binds to the active ___ of the
    Sonic hedgehog protein and allows this paracine factor to diffuse over a range of a few hundred micrometer (___)
  3. The ___ that binds sonic hedgehog also needs cholesterol in order to function.
A

Sonic Hedgehog Protein

N-terminus; cholesterol modification

Patched protein

56
Q

The Hedgehog Family:
Vertebrates have at least 3 homologues of the Drosophila hedgehog gene:

A

desert hedgehog (dhh)
- sertoli cells of the testes

indian hedgehog (ihh)
- gut and cartilage

sonic hedgehog (shh)
- important in embryo development

57
Q

Hedgehog Pathway - Generic Process Summary

A
  1. Hedgehog
  2. Patched
  3. Smoothened
  4. Ci protein made activator
  5. Transcription
58
Q

Are a family of cysteine-rich glycoproteins
- Receptors:

A

Wnt (Wingless-related integration site) Family
- Receptors: Frizzled gene family

59
Q

[Wnt Signalling Pathways]
1.Active in inducing the dorsal cells of the somites to become muscle and is involved in the specification of the midbrain cells

  1. Critical in establishing the polarity of the insect and vertebrate limbs, promoting the proliferation of stem cells.
    - also play several roles in the development of the urogenital organs
  2. Is necessary for kidney development and for female sex determination
A
  1. Wnt1
  2. Wnt proteins
  3. Wnt4
60
Q

[Wnt Family]
Intracellular Pathways:

A
  1. Wnt/B catenin (Canonical)
  2. Wnt/JNK
  3. Wnt/Calcium Dependent (Noncanonical) Pathways
61
Q

Wnt/B catenin (Canonic) Pathway summary process:

A
  1. Wnt
  2. Frizzeled
  3. Disheveled
  4. GSK-3
  5. B-catenin
  6. Transcription
  • Wnt binds to Frizzled receptor family
  • Activates Disheveled
    -Disheveled blocks GSK-3
  • B-catenin released from APC
  • Enters nucleus, associates with LEF/TCFTFs
62
Q

[Wnt/B catenin Pathway]
1. - Tumor suppressor
- targets B-cateninn for degradation

  1. Prevents B-catenin dissociation from APC
A
  1. APC- adenomatosis polypsis coli
  2. GSK-3: Glycogen synthase kinase 3
63
Q

Proteins from the inducing cell interact with receptor proteins of adjacent responding cells without diffusing from the cell producing it.

A

Juxtacrine Signaling

64
Q
  • Important in development and homeostasis
  • Involved in development of sensory hair cells and branched arterial networks
  • Associated with tissue growth and cancer and cell death and tumor suppression
A

Notch Signaling Pathway

65
Q
  1. 4 NOTCH Receptors in Mammals
  2. Ligands of Notch Pathway
A
  1. NOTCH1, NOTCH2, NOTCH3, NOTCH4
    2.- Jagged protein family (JAG1 and JAG2)
    - Delta-like Protein family (DLL1, DLL3, DLL40
66
Q

What are some of the importance of Notch proteins?

A
  • They are extremely important receptors in the nervous system.
  • Involved in the formation of numerous vertebrate organs such as kidney, pancreas, and heart
67
Q

What are some of the importance of Notch proteins?
- In the vertebrate eye, the Interactions between Notch and its ligands regulate which cells become optic ___ and which become ___

A

neurons

glial cells.

68
Q

What are some of the importance of Notch proteins?
- In vertebrate and ___ nervous systems, the binding of ___ tells the receiving cell not to become neural.

A

Drosophila

Delta to Notch

69
Q

The Mechanism of Notch Activity

A
  1. Delta binds to Notch
  2. Binding activates proteolytic cleavage of Notch inner portion
  3. Proteolytic fragment moves to nucleus
70
Q

[The Mechanism of Notch Activity]
Details of 3.) Proteolytic fragment moves to Nucleus

A
  • Displaces repressor
  • Recruits p300 HAT
  • Activates Transcription
71
Q

A signal from the inducing cell is necessary for initiating new gene expression in the responding cell

e.g optic vesicle placed under a new region of __

A

Instructive

head ectoderm

72
Q

___ restrict the cell’s developmental options

A

Instructive interactions

73
Q

In Permissive interactions, The responding tissue has already been ____; needs only an environment that allows the expression of
those traits.

A

specified

74
Q

____ tend to regulate the degree of expression of the remaining developmental potential of the cell.

Example: Many tissues need a solid substrate containing ___ in order to develop.

A

Permissive interactions

fibronectin

75
Q

WHO? transplantation of tissues
Mesenchyme induces epithelial structures

A

Hans Spemann and Oscar Schotté (1932) -

76
Q

____can generate different structures from the same responding tissue.

A

Regional specificity of inductions

77
Q

The specific response to an inducer is determined by the genome of the responding tissue

A

Genetic specificity of induction

78
Q

Cell-Cell Communication
The components of this signal/response system must include:

A

1) A signal
2) A receptor for that signal
3) A mechanism to translate and/or transport the signal
4) A mechanism to translate the signal to a
stimulation (or repression) of gene expression

79
Q

the events within the cell that occur in response to a signal

A

Signal transduction

80
Q

are involved in the formation of numerous vertebrate organs
- kidney, pancreas,and heart

are extremely important receptors in the nervous system

A

Notch proteins

81
Q

Cell-Cell Communication

The components of this signal/response system must include:

A

1) A signal
2) A receptor for that signal
3) A mechanism to translate and/or transport the signal 4) A mechanism to translate the signal to a
stimulation (or repression) of gene expression

82
Q

the events within the cell that occur in response to a signal

A

•Signal transduction

BIO109 (4 decks)

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