Cell Signalling basics Flashcards

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1
Q

What are the three main types of effector proteins? And what do they do?

A
  1. Cytoskeletal proteins - alter shape and movement of cell
  2. Gene regulatory proteins- alter gene expression
  3. Metabolic enzymes - altered metabolism
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2
Q

Name the Four types of INTERcelluar signalling?

A
  1. Contact-dependent cell signalling
  2. Paracrine
  3. Synaptic
  4. Endocrine
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3
Q

What are the four main signalling pathway families in Paracrine signalling?

A
  1. Fibroblast growth factor - utilises RTK pathway
  2. Hedgehog family- (desert, Indian and SONIC) involved in embryonic development
  3. Transforming growth factor- beta (TGF) - cell proliferation
  4. Wnt family
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4
Q

Describe the common types of Wnt signalling, receptors and one Intracellular signalling protein known to mediate such signalling pathways?

A

Wnt pathways- 1. Canonical 2. Non-canonical planar cell polarity 3. Non canonical Wnt/calcium pathway

Frizzled G-protein-coupled receptor, directly activates the cytoplasmic phospho-protein Disheveled

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5
Q

What are the two distinct types of signalling pathways? How immediate are they and what general effect do they have on the cell?

A
  1. Alterations in protein function and 2. Alterations in gene-expression

1st Is fast, seconds to minutes
2nd is slow, minutes to hours

Both alter the cytoplasmic machinery and —> altered cell behaviour/function

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6
Q

What is Acetylcholine?

A

ACh is a ubiquitous neurotransmitter involved in the autonomous nervous system, and acts on both the CNS and the Peripheral nervous system

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7
Q

What are three common effects of ACh neurotransmission?

A
  1. Decreased Cardiac muscle contraction and force, acts via Muscarinic receptor M2 (activated by Muscarine and ACh) - inhibition of V-gated calcium channels, efflux of K+ hyperpolarisation of neutrons= inhibitory effect and decreased cAMP levels
  2. skeletal muscle contraction - via ACh receptors, ligand-gated sodium channels activated —> sodium in muscle cells leads to contraction
  3. Salivary gland secretion - via M1 receptors
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8
Q

What are the 4 most common outcomes of signalling pathways?

A
  1. Survival
  2. Growth and division
  3. Differentiation
  4. Cell death - no signals
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9
Q

Draw AcetylCholine!

A

Not fucking about mate.

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10
Q

Draw the cross section of a typical blood vessel and label appropriately. (Smooth muscle cells, basal lamina, endothelial cells)

A

Yeah.

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11
Q

What effect does Calcium have on the isoforms of a Adenylate Cyclase? And what activates class 2 and 4 of AC’s?

A

3 and 5 are stimulated by Calcium
1 and 6 are inhibited by Calcium

And 2 and 4 are stimulated by Beta-Gamma subunits of the activated G protein (coupled to a GPCR)

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12
Q

What is eNOS?

A

Endothelial Nitric Oxide Synthase. Converts L-Arginine (with NADPH, H, and 02) into Citrulline and NO.

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13
Q

Describe the steps in Vasodilation with associated eNOS.

A
  1. AcetylCholine is released from Synapse of surrounding Nerve cells.
  2. acetylcholine binds and activates Endothelial Nitric Oxide Synthase
  3. eNOS converts L-Arginine into Citrulline and NO, with NAPDH, H and O.
  4. NO diffuses from cell membrane to other surrounding cells
  5. NO binds and activates Guanylyl cyclase producing cGMP
  6. Increased cGMP levels causes decreased Intracellular Calcium concentrations
  7. Activation of K+ channels, leads to hyper-polarisation and relaxation
  8. cGMP-dependent kinase activates Myosin light chain phosphatase, which dephosphorylates Myosin light chains = smooth muscle cell relaxation
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14
Q

Name 5 signal molecules which bind INTRAcellular receptors (hint: RECtv)

A
Retinoic acid
Estradiol 
Cortisol
testosterone
vitamin D3
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15
Q

Detail and draw the structure of an archetypal Nuclear receptor. (Hint has 5 domains)

A
  1. Transcription activating domain at N terminal
  2. DNA-binding domain (DB domain)
  3. The variable sequence hinge domain (links DBD and LBD together)
  4. The ligand binding domain (LBD)
  5. The variable C terminal domain, often inhibited by repression proteins
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16
Q

What are nuclear receptors?

A

Essentially ligand-dependent Transcription factors, which directly bind and alter gene expression of a number of genes upon direct ligand association.

The genes regulated by these Intracellular receptors are highly associated to some diseases, making them a target of many drug companies.

17
Q

What is the typical mass range of Nuclear receptors (kDA)?

A

50-100 kDA

18
Q

What is interesting about the N-terminal, Transcription Activating domain of Nuclear receptors?

A

Sequence Variable region, which contains the weak Activation function 1 (AF1). Which upon ligand binding to the LBD synergies which AF2 of the LBD, to produce a stronger up regulation of gene expression.

19
Q

Describe notable features of the DNA-binding domain of Nuclear receptors

A

Highly conserved domain, contains two Zinc fingers which bind to specific regions called HORMONE response elements (HRE) adjacent of the target genes.

20
Q

Describe the features of the Ligand binding domain of Nuclear receptors! (hint: )

A

Moderately conserved sequence, highly conserved structure.
Consists of alpha helical sandwich fold
1. three anti-parallel alpha helices forming the ‘filling’
2. Flanking alpha helices (the bread) 2 on one side, 3 on other

Contributes to the dimerisation interface of the receptor and binds co-activators or co-repressors.
Also contains AF2 which combines with AF1

21
Q

What are the two types of responses induced by the activation of nuclear receptors?

A
  1. The primary (early) response. E.g. Steroid hormone activates associated nuclear receptor, turns on primary response genes and yields primary response proteins
  2. The secondary (delayed) response. E.g. Primary response proteins turn off primary response genes and turn on secondary response genes yielding secondary response proteins.
22
Q

4 main components in a signalling pathway?

A
  1. Extracellular signalling molecule
  2. Receptor protein
  3. Intracellular signalling proteins
  4. Effector proteins