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Cellular Communication > Cell Comm > Flashcards

Cell Comm Flashcards

1
Q

What is autocrine regulation?

A

A cell communication mechanism in which the signalling molecules bind to receptors located on the cell secreting the signalling molecules

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2
Q

What is paracrine regulation?

A

A cell communication mechanism in which the signalling molecules are secreted into the extracellular space and bind to receptors located on the adjacent cells without passing through the circulatory system

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3
Q

What is a neurotransmitter?

A

A chemical substance released from a neuron and bringing about the transfer of an impulse to another neuron

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4
Q

What is endocrine regulation?

A

A cell communication mechanism in which the signalling molecules are secreted from cells located in secretory glands into the circulatory system. This allows for the signalling molecules to travel over a relatively large distance, eventually binding to receptors located on or in cells of a target organ or tissue.

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5
Q

What happens in ligand-gated ion channels?

A

Agonist binds to receptor causing a conformational change of the receptor which allows the flow of ions from a high to a low concentration, down a concentration gradient. This response occurs in milliseconds.

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6
Q

What is the conformation of ligand receptors?

A

Oligomer - Made up of 5 protein subunits that centrally surround the pore of the ion channel

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7
Q

G Protein Coupled Receptors - Adrenaline binding to Beta-2 Adrenoceptors

A

Adrenaline binds to Beta-2 adrenoceptor causing a conformational change of the receptor. This then causes it to bind to the G alpha-s subunit. This causes the change of GDP to GTP, which causes the G alpha-s to move towards adenylyl cyclase, activating it, which converts ATP to cAMP. This then activates the PKA pathway which inhibits MLCK activity causing bronchodilation. Occurs in seconds. Termination occurs by hydrolysis of GTP to GDP and dissociation of adrenaline. This causes the G alpha-s subunit to move back to its original location, and the Beta-2 receptor to change to its original structure.

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8
Q

G Protein Coupled Receptors - Adrenaline binding to Alpha-1 Adrenoceptors

A

Adrenaline binds to Alpha-1 adrenoceptor causing a conformational change of the receptor. This then causes it to bind to the G alpha-q subunit. This causes the change of GDP to GTP, which causes the G alpha-q to move towards Phospholiase C, activating it, which converts PIP2 to DAG and IP3. This then increases intercellular Calcium concentration causing Vasoconstriction of blood vessels. Occurs in seconds. Termination occurs by hydrolysis of GTP to GDP and dissociation of adrenaline. This causes the G alpha-q subunit to move back to its original location, and the alpha-1 receptor to change to its original structure.

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9
Q

G Protein Coupled Receptors - Adrenaline binding to Alpha-2 Adrenoceptors

A

Adenylyl Cyclase is already activated converting ATP to cAMP resulting in cellular responses. Adrenaline binds to Alpha-2 Adrenoceptor, causing a conformational change. This allows it to bind to the G alpha-i subunit, converting GDP to GTP. This activates the G alpha-i subunit causing it to move towards the adenylyl cyclase, switching it off. The G beta-gamma dimer moves towards the potassium ion channel causing the receptor to change shape, allowing the movement of potassium ions from a high to a low concentration, down a concentration gradient. This causes relaxation of the GI tract. Occurs in seconds. Termination of pathway occurs from hydrolysis of GTP to GDP, causing adenylyl cyclase to switch back on. Adrenaline dissociates and this allows the adrenoceptor to return to its original conformation. The G alpha-i subunit returns back to its original spot as does the G Beta-Gamma dimer does too.

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10
Q

Why does golgi recieve vesicles from endosomes and secretory vesicles?

A

Golgi recycles vesicles

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11
Q

When can proteins be modified?

A

During or after mRNA translation

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12
Q

What is an isoform?

A

Molecule that has the same molecular structure but different formational structure

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13
Q

Proteolysis - Post translation modification what does it do?

A

To make different variations(isoforms) of a protein from single mRNA
To convert a protein to its active form
To enhance proper folding of the protein
To enhance insertion of protein to membranes or lumen of organelles

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14
Q

Covalent addition of molecules(such as acetyl group, methyl group, phosphate group, sugar moieties and small peptides) - Post-translational modification what does it do?

A

To enhance/disrupt interaction with other proteins
To enhance stability or degradation
To enhance transportation

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15
Q

What do you think would happen if insulin are translated from mRNA to its active form?

A

Cell not designed for insulin, could start carrying out that function when it cant

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16
Q

What are enzymes that add phosphate groups called?

A

Kinases

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17
Q

What are enzymes that remove phosphate groups are called?

A

Phosphatases

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18
Q

What is glycosylation?

A

Addition of sugars to the side chains of certain amino acids

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19
Q

What is N-Linked glycosylation?

A

Important for protein folding
Protein targeting (mannose-6-phosphate targets lysosome)
Occurs initially in the ER and is refined in the Golgi

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20
Q

What is O-linked glycosylation?

A

Complementary to phosphorylation and enhance protein-protein interaction
Mostly occur in the Cytoplasm

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21
Q

What are the main post-translational processing types?

A

Proteolysis- Cleaving the peptide allows the fragments to fold into different shapes
Glycosylation - adding sugars is important for targeting and recognition
Phosphorylation - Added phosphate groups alter the shape of the protein

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22
Q

What are challenges for intracellular signal transduction?

A

The presence of extracellular (or intracellular ligand) must be sensed by the cell
Information must be transmitted further into the cell from the ligand-bound sensor
Information must be amplified so that small input signals can yield large changes in a biological output (and random fluctuations/ noise are filtered out)
Feedback mechanisms can influence the overall output of a specific signalling pathway
Information from multiple inputs are often integrated, thereby affecting the final biological output

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23
Q

Intracellular signalling pathways usually follow what … until…?

A

(mostly) follow a linear (or hierarchical) signalling cascade format, where each event leads directly to the activation of the next downstream event. Until a biological change occurs in the cell response to the initial stimulus(e.g cytoskeletal rearrangement, new gene expression, metabolic changes etc.)

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24
Q

What does PKA regulate?

A

PKA regulates the transcription of specific genes

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25
Q

What do hierarchical signalling cascades organised to do?

A

organised in 3D-space by ‘scaffolding’ proteins to enhance the efficiency of the signalling pathway

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26
Q

How are risks of cellullar function being altered by chance minimized

A

Often in biological systems a specific, quantifiable threshold must be reached in order for a biological outcome to occur
Whether or not a signalling pathway reaches the threshold is influenced by a number of different factors that can influence the strength and duration of that signal

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27
Q

When do Prokaryotes express genes?

A

‘If and when’ required so as to conserve energy

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28
Q

What does ‘if and when’ refer to in prokaryote gene expression?

A

Genes that are required for housekeeping : such genes are required all the time and are constitutively expressed
Genes that are switched on or off in response to changes in environmental conditions (e.g. nutrients, temperature); induced or repressed gene expression

29
Q

How can gene expression be regulated?

A

Regulate transcription - predominant in prokaryotes
Hydrolyze mRNA, preventing translation
Prevent mRNA translation at the ribosome
Degrade the protein after it is made
Inhibit the function of the protein

30
Q

What is allosteric regulation?

A

Enzyme reacts with a cofactor- changes conformation of protein which causes it to become more or less active

31
Q

Where does gene expression begin?

A

Begins at the promoter - a sequence of DNA adjacent to the gene where transcription factors bind and RNA polymerase is recruited to initiate transcription

32
Q

What is the role of sigma factor?

A

Sigma factor recognises and ind core promoter elements (-10 and -35 sequences) and recruits RNA polymerase
Core promoter element variants are recognised and bound by specific sigma factors
‘Strong’ promoters confirm to the consensus sequence and initiate transcription frequently (RNA synthesis level determined by initiation and elongation of transcription)

33
Q

What are two regulatory proteins may bind DNA

A

Repressor proteins and activator proteins

34
Q

What are two ways to regulate a metabolic pathway?

A

Allosteric regulation of enzyme-catalyzed reactions allows rapid fine-tuning
Regulation of gene expression (regulation of the synthesis of enzymes) is slower but conserves resources. Usually in bacteria

35
Q

What is an operon?

A

A cluster of genes with a single promoter and transcribed together into a single mRNA. Allows for genes to be co-regulated

36
Q

What does an operon consist of?

A

A promoter
Two or more structural genes
An operator - a short stretch of DNA between the promoter and the structural genes

37
Q

Inducible operon regulation

A

An inducible operon regulated by a repressor protein (default is ‘off’) - metabolic substrate(inducer binds to a repressor) -> repressor changes shape -> does not bind to operator - >transcription

38
Q

Repressible operon regulation

A

A repressible operon regulated by a repressor protein (default is ‘on’) - repressed when co-repressor (metabolic product) binds to its repressor (binding -> repressor changes shape -> binds to operator -> inhibits transcription)

39
Q

What pathways do inducible systems control?

A

Generally control catabolic pathways (metabolic pathway that breaks down molecules (substrate) into smaller units, with the release of energy); turned ‘on’ when substrate is available

40
Q

What pathways do repressible systems control?

A

Anabolic pathways (metabolic pathways that constructs molecules (product) from smaller unit, with energy requirement); turned ‘on’ until product concentration becomes excessive

41
Q

Operon regulated by an activator protein

A

(default is ‘off’): can increase transcription through positive control.
-If high lactose - low glucose, CRP(cAMP receptor protein) binding to the lac operon promoter makes the sigma factor-RNA polymerase promoter binding more efficient, and increases (‘activates’) transcription.

42
Q

What makes a muscle cell and what makes a red blood cell?

A

Differential gene expression regulated by the combination of different transcription factors in that cell determine cell differentiation and identity/function

43
Q

How is gene expression regulated in eukaryotes?

A

In response to extra- or intracellular signals to mount the appropriate cellular response

44
Q

How is gene expression increased or decreased in response to environmental/extra- or intracellular change?

A

Cells have distinct sets of transcription regulators; some of these regulators work to increase transcription, whereas others prevent or suppress it, such that only a fraction of the genes in a cell are expressed at any one time

45
Q

What are potential points for the regulation of gene expression in eukaryotes

A

Remodelling of chromatin - resulting in increased promoter accessibility for transcription to initiate
Transcriptional regulation(pre-mRNA synthesis)
Pre-mRNA splicing (transcript processing)
Transport of the mRNA (from nucleus to cytoplasm)
mRNA stability
Translational control at the ribosome (protein synthesis)
Post-translational modification of proteins (e.g. phosphorylation, acetylation, ubiquitination)
Protein degradation (proteasome)

46
Q

Regulation of transcription in eukaryotes

A

General (basal) transcription factors
Transcriptional activator or repressor proteins

47
Q

General (basal) transcription factors

A

General (basal) transcriptional factors binding the core DNA promoter (starting with TFIID) to recruit RNA polymerase; required at every gene (basal level of transcription)
Efficiency of binding of GTFs to the core promoter DNA sequences determines levels of transciption (promoter stength)

48
Q

Transcriptional activator or repressor

A

Transcriptional activator or repressor proteins bind to DNA regulatory elements (promoter proximal or distal sequences), to enhance or repress transcription levels directed by the basal transciption factors and RNA polymerase at the core promoter

49
Q

How is eukaryotic gene transcription regulated?

A

Some regulatory sequences are commmon to promotes of many genes; recognized by transcription factors in all cells (generally, at promoters of constitutively expressed genes, eg ‘housekeeping genes’)
Some regulatory sequences are specific to a few genes and are recognized by transcription factors found only in certain tissues (embryogenesis, development and differentiation (specialization) of cells; tissue specifi)

50
Q

How is gene expression coordinated in eukaryotes?

A

Gene expression is coordinated if they have the same regulatory sequences that bind the same regulatory protein (‘drought - sensitive’ transcription factor). (no operons in eukaryotes)

51
Q

Hormone - general characteristics

A

Any substance elaborated by one cell to regulate another cell. May be delivered by autocrine, paracrine, or endocrine routes
The biological response is generally the result of an amplification of a signal transduction cascade
Many hormones can evoke cellular and tissue effects at very low concentrations
Most hormones have effects on multiple targets in the body
Hormonal duration of action can vary from seconds to days depending upon the receptor and signalling system that is activated

52
Q

Peptide hormones

A

Hydrophilic and are transported unbound or ‘free’ in blood plasma without the need of blood carrier proteins
This results usually in very short biological half-lives (this refers to the amount of time it takes for a concentration of hormone (wt/v) in plasma that decrease by 1 half)
Largest category of hormones produced
Many bind to membrane-bound receptors (GPCRs and Kinase-linked receptors)
Secreted by pituitary, parathyroid, heart, stomach, liver, kidneys
Synthetic peptide hormones (e.g recombinant human insulin) cannot be administered orally as they are very susceptible to degradation in the GI tract
May be composed of a ring structure due to disulfide bonds as in the case of somatostatin
May be composed of 2 chains such as insulin held together by disulfide bonds

53
Q

Peptide hormone structure (insulin)

A

Mature mRNA is translated into preproinsulin containing a ‘leader’ sequence followed by A, B and C domains
The leader sequence is cleaved in the ER lumen resulting in proinsulin
Proteases cleave the proinsulin at 2 sites removing the C peptide. The A and B chains remain connected by disulfide bonds
Mature insulin is stored in secretory vesicles until released following a signalling response. Release by exocytosis is dependent upon increasing intracellular Ca2+ concentration

54
Q

Cellular energy status is linked to Insulin secretion in the pancreatic Beta-cell

A

Elevation of blood glucose concentration -> increased diffusion of glucose into the beta cell by facilitated transport (GLUT2) -> Phosphorylation of glucose by glucokinase -> glycolysis of glucose-6-phosphate in mitochondria yielding ATP -> Increased ATP/ADP ratio within cell closes ATP-sensitive potassium channels causing membrane depolarisation -> opening of voltage-activated calcium channels increases intracellular calcium that triggers insulin secretion

55
Q

What is signal transduction?

A

The biomechanical mechanism responsible for transmitting extracellular signals across the plasma membrane and throughout the cell
Essential in the communication between cells and the environment, leading to the appropriate physiological response
Process which changes information into a ‘chemical signal’
Often ends with covalent or non covalent modification of intracellular target proteins

56
Q

Receptor proteins in eukaryotes - cell surface versus intracellular

A

Water soluble (polypeptides, amines) signalling molecules (‘first messengers’) bind cell surface receptors
Cell-cell communication mediated by lipophilic ligands derived from cholesterol (steroid hormones), pass freely through the cell membrane and bind to intracellular receptors (~60 genes encode such proteins in humans)

57
Q

Lipids function in cell signalling

A

Their hydrophobic property of lipids contributes to their functions as high-affinity stereospecific ligands that bind to hydrophobic pockets in receptor proteins

58
Q

What are steroid hormones?

A

Cholesterol-derived ligands for intracellular (nuclear) receptor proteins which mediate hormone signals by altering the expression of specific genes
Potent signalling molecules that have a critical role in - cell development
-reproductive biology
-organismal physiology

59
Q

How do steroid hormones exit endocrine cells?

A

Steroid hormones exit endocrine cells by diffusing out across membranes, where they bind transport proteins (carrier proteins) that keep them soluble (in the blood stream), i.e. hormones can act at a distance (‘systemic’) and contact receptor proteins in the cells of target tissues

60
Q

How do steroid hormones enter cells?

A

Diffuse into target cells.
Typically bind to hormone receptors in the cytoplasm and move to the nucleus
The hormone-bound receptor in the nucleus then triggers changes in gene expression, by serving as transcription factors interacting with a specific DNA-binding protein or a response element in the DNA

61
Q

Nuclear/Intracellular receptor signalling is governed by what?

A

The cell-specific physiological responses controlled by intracellular/nuclear receptors is governed by three parameters
- Cell specific expression of nuclear receptors
- Localized bio-availability of ligands
- Differential accessibility of target gene DNA sequences in chromatin to nuclear receptor binding

62
Q

Nuclear/Intracellular receptor signalling general mechanism

A
  • Binding of lipophilic first messengers to ligand binding domain which can occur with or without DNA present. Can occur in cytoplasm (and translocation into the nucleus) or the nucleus
  • Ligand activated nuclear receptors (conformations change; loss of inhibitory proteins) bind directly or indirectly to hormone regulatory elements in the DNA and recruit co-regulatory proteins which alter transcription rates (through acetylation or deacetylation of histones in chromatin, altering accessibility of DNA for transcription)
63
Q

Glucocorticoid receptor

A

Head-to-head homodimers, enabling them to bind to inverted repeat DNA sequences
90kDa protein (required for lung development, carbohydrate metabolism in the liver, modulation of (anti-)inflammatory responses and neuronal signalling in the brain)

64
Q

What is a cytokine?

A

Any class of immunoregulatory proteins (such as interleukin or interferon) that are secreted by cells especially of the immune system

65
Q

What do cytokines do?

A

Cytokines are small secreted proteins and peptides that can modulate the behaviour of cells
Regulate - hematopoiesis, immunity and inflammation
Four major families - Interferons for anti-viral activity, Tumour necrosis Factor a pro-inflammatory cytokine, Chemokines which control and direct cell migration, and interleukins which have various functions

66
Q

Cytokine receptors are multimeric. What does this mean?

A

They have shared signal-transducing subunits
Have a unique high affinity, ligand-binding subunit

67
Q

What is the difference between kinase linked receptors and cytokine receptors?

A

Cytokine receptors do NOT possess intrinsic catalytic activity

68
Q
A

Cellular Communication (1 decks)

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