Cell Signalling Flashcards

1
Q

During the process of embryonic development, undifferentiated precursor cells differentiate and organize into …

A

The complex structures found in functional adult tissues

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2
Q

The intricate process of embryonic development requires cells to…

A

Proliferate, differentiate, and migrate to determine the final size and shape of the developing organs

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3
Q

Disruption of signalling pathways can result in

A

Human developmental disorders and birth defects

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4
Q

Cell signalling is part of a complex system of communication that governs

A

Basic cellular activities and coordinates cell actions

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5
Q

Signal transduction

A

Any process by which a cell converts one kind of signal or stimulus into another

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6
Q

Many enzymes are switches “on” or “off” by

A

Phosphorylation and de phosphorylation

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7
Q

6 types of cell changes from zygote to human

A
  1. Proliferation (mitosis)
  2. Differentiation (daughter cells are not same as precursor)
  3. Migration (blood cells)
  4. Growth
  5. Transformation (change to serve other function)
  6. Death (apoptosis)
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8
Q

Can a somatic skin cell become a human

A

No, it is not potent. Zygote has potency meaning it is not so differentiated good one specific function.

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9
Q

Totipotent

A

Cells that have high potential to grow to a human (zygote)

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10
Q

All of the 6 types of cell changes are caused by

A

Cell signalling

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11
Q

Transcription factors

A

Factors or proteins that affect transcription by binding to DNA and cause up or down regulation of genes.

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12
Q

Protein modification and types

A

Addition or removal of chemical molecules from proteins

Cotranslational protein modification: protein mod during translation

Post translational: protein mod after translation (phosphorylation and de phosphorylation)

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13
Q

Amino acid structure

A

Contains an N terminis and a C terminis. N is our first and starts with MET (start codon) but is cleaved off in protein modification.

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14
Q

Which amino acid phosphorylation by protein kinase

A

Ser, thr, Tyr

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15
Q

What protein removes phosphates

A

Phosphatases

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16
Q

Kinases add phosphsate from

A

ATP

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17
Q

Protein kinases can be ….

A

Tyrosine kinases= receptor tyrosine kinase(RTK)(receptors on cell membrane) or non receptor tyrosine kinases (in cytoplasm or nucleus)

Or

Serine/Therein kinases

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18
Q

Conformational change

A

3D structure of protein changes by adding a chemical or molecule

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19
Q

Protein domains

A

Extracellular
Transmembrane
Intracellular

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20
Q

Conformational change process (basic)

A

Conformational change goes through protein domains, expose site, activated receptor and recruits target protein, stimulates A and activates A, then B, then C, then activation of TF, then translocation to nucleus, then regulates gene expression.

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21
Q

Types of intracellular signalling

A

Autocrine: signalling molecule produced by cell with receptor for it

Paracrine: cells in Visconti’s of signalling cell have receptors

Endocrine: signals move through body fluids to any tissue site with cells with receptors

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22
Q

During embryogenesis the differentiation of many different cell types is regulated through a relatively restricted set of molecular signalling pathways:

A
  • morphogens
  • notch/ delta
  • transcription factors
  • receptor tyrosine kinases (RTK)
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23
Q

Two classes of proteins required for intercellular communication are

A

Gap junctions and cell adhesion molecules

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24
Q

Gap junctions

A

Means for cells to directly communicate to each other

  • Gap junction intercellular communication
  • pore sized only allowing smaller molecules like ATP and ions
  • important for regionalization
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25
Q

Gap junctions are made up of

A

6 Connexon Hemi channels

-each has 4 transmembrane domains with the N and C terminus in the cytoplasm

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26
Q

Cell adhesion molecules

A

Adhere cells

  • have large extracellular cadherin domain that interact with extracellular matrix and other extracellular domains of other cells.
  • critical to regulate cell layers (endothelial and epidermal separation) and regulate cell migration, and neuron growth
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27
Q

Extracellular Cadherin domain connected by

A

Calcium binding site

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28
Q

Cytoplasmic domain of cadherin has what proteins

A

P120, Beta- catenin, alpha catenin and actin cytoskeleton

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29
Q

Yep types of cell adhesion molecules

A

Cadherin and immunoglobins

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30
Q

Example of immunoglobin superfamily

A

Neural cell adhesion molecule

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31
Q

Morphogens and examples

A

Diffusible molecules that specify which cell type will be generated at a specific anatomic location and direct the migration of cells and their processes to their final destination

Retinoids acid, transforming growth factor beta (TGF-B)/bone morphogenetic proteins (BMPS) and the hedgehog and Wnt protein families

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32
Q

Retinoic acid

Excessive amount causes

A

The anterior (rostral, head)/ posterior (caudal, tail) or anteroposterior (AP) axis of the embryo is crucial for determining the correct location for structures such as limbs and for the patterning of the nervous system

Retinoic acid posteriorizes the body plan. Therefore excessive or inhibition of its degradation leads to truncated body axis where structures have a more posterior nature

Metabolizes vitamin A

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33
Q

Insufficient retinoic acid or defects the enzymes such as retinal aldehyde dehydrogenase will lead to

A

A more anteriorized structure

34
Q

At a molecular level, retinoic acid binds to its receptors ________ the cell and _____ them

A

Inside

Activates them

35
Q

Retinoic acid receptors are

A

Transcription factors and therefore their activation will regulate the expression of downstream genes such as HOX genes

36
Q

Dietary vitamin A (retinol) metabolism

A

Retinol becomes retinal from retinol dehydrogenase. Retinal becomes retinoic acid from retinal dehydrogenase. (Oxidation reaction) Retinoic acid becomes inactive metabolites from CYP26

Cellular retinal binding proteins and cellular retinoic acid binding proteins can inhibit such reactions.

37
Q

6 regulators of retinoic acid

A
  1. Intake
  2. Retinol dehydrogenase
  3. Cellular retinal binding proteins
  4. Retinal dehydrogenase
  5. Cellular retinoic acid binding protein
  6. CYP26

Mutations in any can cause changes in embryologically development but process is highly regulated

38
Q

Transforming Growth Factor beta/BMP

A

Members of the TGF-beta superfamily include TGF-beta, BMP’s, activin and nodal.

These molecules contribute to the establishment of dorsiventral patterning, cell fate decisions, and formation of specific organs, including the nervous system, kidneys, skeleton, and blood.

In humans there are 3 TGF-beta idk forms

TGF-beta 1, TGF-beta 2 and TGF-beta 3

39
Q

TGF-beta pathway A

A

The type 2 TGG-beta receptor subunit or TbetaR|| is most likely active

40
Q

TGF-beta pathway B

A

On binding of ligand TGF-beta to TbetaR-||, a type 1 receptor subunit is recruited to form a heterodimeric receptor complex, and the TbetR-| kinase domain is transphosphorylated (-p). Signalling from the activated receptor complex phosphorylates R-SMAD’s, which then bind to a co-SMAD, then translocates from the cytoplasm to the nucleus and activated gene transcription with cofactors.

41
Q

Sonic hedgehog (Shh) primary receptor and absence/ presence of shh

A

Primary receptor for shh is Patched (PTCH), a 12- transmembrane domain protein that, in the absence of shh, inhibits smoothened (Smo), a seven-transmembrane domain G protein linked protein, and downstream signalling to the nucleus

In the presence of Shh, Ptc inhibition is blocked and downstream events follow, including nuclear translocation of Gli, with transcriptional activation of target genes, such as Ptc-1, Engrailed and others.

42
Q

Shh and BMP’s are expressed in __________ gradients in the developing ____ tube

A

Opposite

Neural

Moving from dorsal to ventral there is a growing gradient of Shh. Moving from ventral to dorsal, there is a growing gradient of BMP’s

At any anatomical location of neural tube, there are different levels of Shh and BMP’s and therefore differentiates regions and cells.

The gradients determine dorsal-ventral cell fates

43
Q

In the neural tube, Shh is secreted by the…… and BMP’s (Bone morphogenetic proteins) are secreted by the…

A

Notochord and floorplate

Roofplate and overlying epidermis

44
Q

Wnt/beta-Catenin

A

The Wnt-secreted glycoproteins are vertebrate orthologs of the Drosophila gene Wingless (if mutated flies don’t develop wings)

The 19 Wnt family members control several processes during development including establishment of cell polarity, proliferation, apoptosis, cell date specification, and migration

45
Q

Receptor of Wnt’s

A

Specific Wnts’s being to one of10 different Frizzled (Fzd) 7 transmembrane domain cell surface receptors, and with low density lipoprotein receptor-related-protein (LRP5/6) co receptors, thereby activating downstream intracellular signalling events.

46
Q

Wnt/beta-catenin pathway

A

A) in absence of Wnt ligand binding to Fzd receptor, beta-catenin is phosphorylated by a multi protein complex (axin, GSK-3, APC) and targeted for degradation. GSK-3 is not phosphorylated. Target gene expression is repressed (inhibited) by T-cell factor (TCF).

B) When Wnt binds to Fzd, LRP core rotors are recruited, Dishevelled (DVL) is phosphorylated and activates to phosphorylated GSK-3 making it inactive and beta-catenin then accumulates in the cytoplasm. Some beta-catenin enters the nucleus to activate target gene transcription.

47
Q

NOTCH-DELTA Pathway purpose

A

This pathway often specifies which cell fate precursor cells will adopt

Integral for cell fate determination, including maintainable of stem-cell niches, proliferation, apoptosis and differentiation

Ligand-receptor binding triggers proteolytic events (protein breakage) leading to the release of the NOTCH intracellular domain (NICD). When the NICD translocates to the nucleus, a series of intranuclear events culminated in the induction of expression of hairy-enhancer of split, an HLH transcription factor that maintains the progenitor state by repressing pro neural basis HLH genes

48
Q

Proteases and peptidases cleavage

A

Cut into small pieces

Cut at specific place

49
Q

Domains of NOTCH receptor

A

NECD
NTMD
NICD

50
Q

Differentiating cell

Progenitor cell

A

Cells already on path to be a particular cell

Stem cells with high potency to be something

51
Q

NOTCH/Delta signalling pathway

A

Differentiating cell is signalling cell with its ligand DELTA/Jagged which can bind to NOTCH. In progenitor cells, activation of NOTCH signaling leads to cleavage of the NICD. NICD translocates to the nucleus, binds to a transcriptional complex, and activates target genes such as Hes1, that inhibit differentiation.

Binds, exposes site where ADAM can cleave ECD, so change in conformation so presenilin cleave TMD so NICD can move to nucleus

52
Q

NOTCH has different _____ sites

A

Cleavage

If Delta/Jagged bind to protein it alters confirmation and exposes cleave site so ADAM can cleave protein in extracellular space. Presenilin can cleave in transmembrane domain, and Furin can cleave intracellular.

53
Q

Transcription Factors

A

Belong to a large class of proteins that regulate the expression of many target genes, either through activation or repression mechanisms .

-will bind to specific nucleotide sequences in the promoter/ enhancer regions of target genes and regulate the rate of transcription of its target genes via interacting with accessory proteins

54
Q

Transcription complex

A

Transcription factor+target genes+accessory proteins

55
Q

Histones and his tone modification

A

Positively charged nuclear proteins around which genomic DNA is cooked in units to tightly pack it in Structures known as nucleus ones within the nucleus

Histone modification is used by TF to regulate activity of their target promoters. Ex: phosphorylation, acetylation and methylation

56
Q

DNA is less tightly bound to _____ histones

A

Acetylated, allowing more access of TF and other proteins to the promoters on target genes

TF can modify Histone acetylatioj by recruiting Histone acetyltransferases or Histone deacetylases.

57
Q

HAT’s

A

Histone acetyltransferases

Controls Histone acetylation status

can add acetyl groups

58
Q

HDAC’s

A

Histone deacetylases can remove acetyl groups

59
Q

Phosphorylation of histones leads to

A

Opening of the chromatic structure and activation of gene transcription

60
Q

Epigenetic modifications alter the transcriptional properties of chromatin pathways

A

A) in areas of transcriptionally inactive chromatin, the DNA is tightly bound to the histone cores. The histones are not acetylated or phosphorylated. HDAC’s are active and HAT’s and histone kinases are inactive. (Highly methylated which suppress gene expression)

B) in areas of transcriptionally active chromatin, the DNA is not tightly bound to the histone core, and the DNA is unmethylated. The histone proteins are acetylated and phosphorylated. HDAC’s are inactive and HAT’s and histone kinases are active

61
Q

Transcription factor examples

A
  • HOX proteins (mutations in the DNA-BD of the NKX2-5 cardiac defects)
  • PAX genes (ophthalmic defects)
  • Basic Helix-Loop-Helix TF (muscle differentiation)
62
Q

Receptor Tyrosine Kinases (RTKs)

A

Many growth factors signal by binding to and activating membrane bound RTKs. These kinases are essential for the regulation of cellular proliferation, apoptosis, and migration as well as processes such as the growth of new blood vessels and axonal processes in the nervous system.

63
Q

Receptor tyrosine Kinase signalling pathways

A

A) in absence of ligand, the receptors are monomers and are inactive.

B) on binding of ligand (double) the receptors dimerize (bind together) (ligand-mediated dimerization) and trans phosphorylation occurs, which activates downstream signalling cascades.

Two single ligands can bind to two RTKs and can a conformational change that causes the two RTK’s to have affinity for each-other and cause receptor mediated dimerization

64
Q

Mesodermal cells upon activation of RTK

A

Brings mesodermal cells that differentiate together and outer areas become epithelial and inner become blood cells making up an early circulatory system!

65
Q

Stem cell differentiation

A

Adult or embryonic stem cells can divide symmetrically, giving rise to two equivalent daughter stem cells (vertical division) or asymmetrically, giving rise to a daughter stem cell and a nervous system progenitor cell (horizontal division)

66
Q

Stem cells and induced pluripotent stem cells (IPS) have the capacity for___

A

Self renewal, cell death, and becoming progenitors.

  • progenitor cells have a limited ability for self renewal but can differentiate into various cell types or undergo cell death
  • adult differentiated somatic cells, such as skin fibroblasts, can be reprogrammed into IPS with the introduction of the master transcription factors SOX2, OCT3/4 or KLF4.
67
Q

IPS

A

Induced pluripotent stem cells

  • develop week 3 when germ layers or defined.
  • are 3 types of IPS- ectoderm, endoderm and mesoderm. Each stem cell can make all the cells of its germ layer.
68
Q

Totipotent
Pluripotent
Multi potent

A

Zygote (can make all cells)
IPS (can make many cells)
Can make few cell types (adult bone marrow, skin etc.

69
Q

Vitamin A caused birth defects/ diseases due to abnormal signalling

A

CNS: spina bifida
Eyes: anopthalmia
Face: cleft palate, harelip
Ear: accessory ears
Urogenital system: cryptorchidism, ectopic ovaries
Heart: aortic arch defects, incomplete ventricular separation

70
Q

TGF-beta family caused birth defects/ diseases due to abnormal signalling

A

Affects nervous system, kidneys, skeleton and blood

71
Q

Hedgehog caused birth defects/ diseases due to abnormal signalling

A

Brain defect: holoprosencephaly, Pallister syndrome, Gorlins Syndrome

72
Q

Wnt/beta-Catenin pathway caused birth defects/ diseases due to abnormal signalling

A

Williams-Beuron sundrome

Osteoporosis-pseudoglioma syndrome

73
Q

Notch-Delta pathway caused birth defects/ diseases due to abnormal signalling

A

Alagille syndrome, CASASIL

74
Q

Transcription factors caused birth defects/ diseases due to abnormal signalling

A

Disorders of chromatin remodelling: Rett, Rubinstein-tayabi, alpha-thalassemia/X-linked mental retardation

75
Q

Homeobox proteins caused birth defects/ diseases due to abnormal signalling

A

Cardiac atrial-septal defects and lissencephaly syndrome

76
Q

Pax gene caused birth defects/ diseases due to abnormal signalling

A

Occular defects, alveolar rhabomyosarcoma, waardens syndrome

77
Q

Receptor Tyrosine Kinase caused birth defects/ diseases due to abnormal signalling

A

Milroy disease, cancer

78
Q

MET VS EMT in adhesion molecules

A

More adhesion

Less adhesion

79
Q

______ posteriorizes body and specifies heart tube dilations

A

Retionic acid

80
Q

Examples of RTK

A

VEGF, IGFR, EGFR, RET, MET

81
Q

FGF8 specifies which body side

A

LEFT

82
Q

Microglial and macroglial cells are derived from?

A

Mesoderm

Ectoderm