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BIO230 Final > Week 10 > Flashcards

Week 10 Flashcards

1
Q

How do cells communicate with each other?

A
  • concepts in cell signaling
  • signaling via small molecules
  • signaling via protein modifications
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2
Q

What is the primary role of signaling in cells?

A

essential for all life as it allows cells to sense and respond to their environment and communicate with each other

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3
Q

What are extracellular signaling molecules?

A

any molecules that can transmit signals between cells (ions, hormones, proteins, and gases)

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4
Q

What is a receptor in cell signaling?

A

binds a signaling molecule (ligand) to initiate a cellular response

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5
Q

What is a ligand?

A

a signaling molecule that can be bound by a receptor

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6
Q

What are intracellular signaling molecules?

A

any molecules that can transmit a signal within a cell, including ions, metabolites, and proteins

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7
Q

What are secondary messengers?

A

non-protein small intracellular signaling molecules that amplify the signal received by the receptor

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8
Q

What are effectors in cell signaling?

A

molecules that receive signals and change cell behavior

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9
Q

What do input and output refer to in a signaling pathway?

A

The start/end of the pathway

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10
Q

What do upstream and downstream mean in the context of signaling pathways?

A

the relative positions in the pathway

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11
Q

What are the primary types of short-distance signaling?

A
  • contact-dependent
  • paracrine
  • autocrine
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12
Q

What is contact-dependent signaling?

A

two cells must be very close to connect a membrane-bound signal in the signaling cell to a membrane-bound receptor in the target cell

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13
Q

What is paracrine signaling?

A

a signaling cell releasing a local diffusible signal that affects nearby target cells

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14
Q

What is autocrine signaling?

A

a cell secretes a diffusible signal that acts on itself

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15
Q

What factors can restrict the movement of signaling molecules?

A
  • Internalization by cells
  • Degradation or destruction
  • Limited diffusion
  • Receptor expression
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16
Q

What are the primary types of long-distance signaling?

A

Synaptic and endocrine

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17
Q

What is synaptic signaling?

A

a neuron extends an axon to reach and make close contact with a distant target cell

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18
Q

What is endocrine signaling?

A

an endocrine cell secretes hormones into the bloodstream for long-range distribution in the body

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19
Q

What are receptors in the context of cell signaling?

A

proteins that bind to specific extracellular signaling molecules (ligands) to facilitate communication between cells

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20
Q

What must a target cell express to receive a signal?

A

the specific receptor protein that corresponds to the signaling molecule (ligand) to be able to receive the signal

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21
Q

What happens when a ligand binds to a receptor?

A

activates the receptor, initiating a signaling cascade

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22
Q

What are the types of receptors mentioned in class?

A
  • cell surface receptors
  • intracellular receptors
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23
Q

What role do many signaling pathway components play in cellular communication?

A

act like molecular switches, enabling cells to rapidly respond to changes in their environment

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24
Q

What are the common types of changes that occur during signaling?

A

involves rapid and reversible changes to proteins:
- Different protein interactions
- Increase/decrease in enzyme activity
- Changes in subcellular localization
- Protein synthesis or degradation

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25
Q

What are the common molecular mechanisms that facilitate changes in signaling pathways?

A
  • Phosphorylation
  • GTP-binding
  • Ubiquitination
  • Other small molecule binding
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26
Q

Why is it important for signaling pathways to be turned “off”?

A

if a signal is always on or off, it becomes unhelpful

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27
Q

What is the role of a protein kinase in protein phosphorylation?

A

adds a phosphate group to a protein

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28
Q

What function does a protein phosphatase serve in the context of protein phosphorylation?

A

removes a phosphate group from a protein

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29
Q

How can phosphorylation affect a protein?

A
  • can change a protein’s structure or charge
  • affect its activity, interactions, or localization
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30
Q

What is the typical effect of phosphorylation on a protein or signaling pathway?

A

usually turns a protein or signaling pathway “on,” but there are exceptions

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31
Q

What is the role of GEFs (guanine nucleotide exchange factors) in GTP-binding protein signaling?

A
  • help to exchange GDP for GTP
  • activating the GTP-binding protein
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32
Q

What do GAPs (GTPase-activating proteins) do in the context of GTP-binding proteins?

A
  • activate the GTPase activity
  • promoting the hydrolysis of GTP to GDP
  • turns the signaling pathway “off.”
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33
Q

How does GTP-binding affect protein function?

A

activity, interactions, or localization

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34
Q

What are the roles of E1, E2, and E3 ligases in ubiquitination?

A

enzymes that help activate the small protein ubiquitin and facilitate its attachment to a target protein.

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35
Q

How does ubiquitination affect a target protein?

A

change a target protein’s activity, localization, or stability

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36
Q

What are some functions of ubiquitination?

A
  • multiubiquitylation: endocytosis
  • polyubiquitylation: proteasomal degradation
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37
Q

Name four examples of secondary messengers.

A

1) Cyclic AMP (cAMP)
2) Calcium ions (Ca2+)
3) Diacylglycerol (DAG)
4) Inositol triphosphate (IP3)

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38
Q

What type of signaling is characterized by very fast communication, occurring in fractions of a second?

A

Synaptic signaling.

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39
Q

What is the primary reason for the slow nature of endocrine signaling?

A

It requires blood circulation to distribute the signaling molecule, which can take minutes or longer.

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40
Q

What types of cellular changes are considered slow in signaling pathways?

A

transcription and translation

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41
Q

What type of cellular changes occur rapidly in signaling pathways?

A

to protein function

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42
Q

Which type of cellular change is the fastest in signaling pathways?

A

membrane potential

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43
Q

Can a single signal trigger both fast and slow responses in a cell?

A

yes

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44
Q

What is the role of inhibitory steps in signaling pathways?

A

important parts of signaling pathways as they influence gene expression by regulating transcription regulators and inhibitors

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45
Q

How is the protein kinase activated in signaling pathways?

A

by an upstream signal which phosphorylates the inhibitor protein

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46
Q

What happens after the inhibitor protein is phosphorylated in signaling pathways?

A

leads to activation of the transcription regulator

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47
Q

How does the inhibitor protein function in signaling pathways?

A
  • normally inhibits the transcription regulator
  • When the inhibitor is inhibited, the transcription regulator becomes active
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48
Q

What role does feedback play in signaling pathways?

A

creates a loop in the signaling pathway, allowing the pathway to remain active even when the original signal is no longer present

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49
Q

What happens to a signaling pathway without feedback?

A

the pathway would only be “on” when the signal is present

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50
Q

How does positive feedback work in signaling pathways?

A

output of the pathway enhances the activity of the pathway

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51
Q

How does negative feedback work in signaling pathways?

A

output of the pathway inhibits its own activity

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52
Q

What is one key characteristic of positive feedback in biological systems?

A

can create an “all-or-none” switch, where a process continues even after the initial stimulus is removed

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53
Q

In the context of positive feedback, what happens when a stimulus activates component A?

A
  • A activates B
  • Bactivates more A
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54
Q

How does positive feedback affect output intensity?

A

It increases the output intensity.

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55
Q

What initiates the feedback loop in the signaling pathway?

A
  • stimulus activates A
  • A activates B
  • B deactivates A
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56
Q

What is the effect of a long delay in the feedback loop?

A

creates an oscillating output in the signaling pathway

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57
Q

What occurs during a short delay in the feedback mechanism?

A

results in decreased output intensity (adaptation or desensitization)

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58
Q

How can negative feedback be achieved?

A
  • different mechanisms
  • negative feedback
  • delayed feed-forward
  • receptor inactivation
  • receptor sequestration
  • receptor destruction
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59
Q

Why do cells usually receive multiple signals at once?

A

to integrate various inputs that are crucial for their survival and proper functioning

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60
Q

What additional signals might be required for cell growth?

A

require growth factors and nutrients to stimulate growth and division

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61
Q

How can the same signal have different effects on different cells?

A
  1. same receptor, different downstream signals/effectors
    - acetylcholine signals the same receptor on the heart pacemaker cell and salivary gland cell, but the heart decreases rate of firing, and salivary promotes secretion
  2. Different receptor
    - acetylcholine binds to different receptors and triggers muscle contractions
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62
Q

How can signals be specific in a complex cellular environment?

A
  • signaling complexes
  • coincidence detectors
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63
Q

What are scaffold proteins?

A

proteins that bind to intracellular signaling proteins to organize and facilitate signaling complexes

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64
Q

What is the purpose of scaffolding proteins?

A
  • limit protein movement
  • ensure signals are passed in order
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65
Q

Can scaffold proteins activate signaling pathways without a signal?

A

yes

66
Q

When do some scaffolds assemble in signaling pathways?

A

once signaling is activated

67
Q

How does the perception of a signal affect receptor modifications?

A

modifies the receptor through processes such as phosphorylation

68
Q

What happens to intracellular signaling molecules in relation to receptor modifications?

A

bind to the modifications of the receptor

69
Q

How do PIPs modify membrane lipids?

A

The perception of a signal modifies the membrane lipids through the phosphorylation of phosphoinositides

70
Q

What is the significance of the phosphorylation of PIPs?

A

creates specific binding sites for intracellular signaling molecules

71
Q

What types of molecules do SH2 and PTB domains bind to?

A

bind to phosphorylated tyrosines

72
Q

What is the function of SH3 domains?

A

bind to proline-rich sequences

73
Q

What do PH domains specifically bind to?

A

bind to phosphoinositides

74
Q

How are protein interaction domains utilized in different proteins?

A

can be mixed and matched in different proteins

75
Q

What role do protein interaction domains play in cellular signaling?

A

help scaffolds assemble

76
Q

Do all protein interactions require phosphorylation?

A

No, protein interactions do not require phosphorylation like SH3 or other domains

77
Q

Which protein interaction domains require phosphorylation to facilitate protein interactions?

A

SH2 and PTB domains

78
Q

What is a coincidence detector in cellular signaling?

A

a protein that requires multiple signals to become active

79
Q

How many phosphorylation sites can Protein Y have?

A

two distinct sites

80
Q

What happens when only one of the signals (A or B) is present?

A

it can trigger phosphorylation at only one site on Protein Y, but not both

81
Q

Under what condition is Protein Y considered active?

A

if it has received phosphorylation events from both signals

82
Q

Why is Protein Y described as a coincidence detector for pathways A and B?

A

it requires the simultaneous presence of signals A and B to be phosphorylated at both sites

83
Q

What are the mechanisms of small molecule signaling?

A
  1. independent of plasma membrane proteins
  2. through ion channels
  3. downstream of G-protein-coupled receptors
84
Q

What type of molecules can passively diffuse into cells?

A

Small, hydrophobic molecules

85
Q

Can you name two examples of small, hydrophobic molecules that can diffuse into cells?

A

Steroid hormones and nitric oxide (NO)

86
Q

What type of signaling molecules do intracellular receptors bind?

A

small, hydrophobic signaling molecules

87
Q

How do small hydrophobic signaling molecules move through the extracellular space?

A

transported by carrier proteins to help them move

88
Q

What happens to small hydrophobic signaling molecules once they reach the target cell?

A

released from the carrier proteins and diffuse into the target cell

89
Q

What type of proteins do these signaling molecules often bind to within the cell?

A

often bound by nuclear receptor superfamily proteins within the cell.

90
Q

What is the function of the N-terminal domain in nuclear receptor superfamily proteins?

A

The N-terminal transcription-activating domain activates transcription of target genes

91
Q

What role does the middle DNA-binding domain play in nuclear receptors?

A

binds to the promoters of specific target genes

92
Q

What is the function of the C-terminal ligand-binding domain in nuclear receptor superfamily proteins?

A

binds to small hydrophobic signaling molecules

93
Q

What are “orphan” nuclear receptors?

A

bind unknown ligands and are classified into this category due to their lack of identified signaling molecules

94
Q

What happens when a ligand binds to a nuclear receptor superfamily protein?

A

causes a conformational change in the protein

95
Q

What is the role of the DNA-binding domain in nuclear receptor superfamily proteins after the ligand binds?

A

becomes free to bind to promoters of target genes

96
Q

What occurs to inhibitory proteins upon ligand binding to nuclear receptor superfamily proteins?

A

Inhibitory proteins are released

97
Q

What is Nitric Oxide (NO) synthesized from?

A

arginine

98
Q

How quickly does Nitric Oxide (NO) act in the body?

A
  • fast and locally-acting due to its instability
  • a half-life of approximately 5-10 seconds
99
Q

What is the mechanism by which Nitric Oxide (NO) signals to nearby cells?

A

diffuse out of endothelial cells and activate signaling in smooth muscle cells

100
Q

What is Guanylyl cyclase?

A

an enzyme that acts as both a receptor and an effector in smooth muscle cells

101
Q

How does light differ from traditional ligands in signaling?

A
  • Light is not a traditional ligand because it does not bind to receptors
  • it can initiate signaling events through photoreceptors
102
Q

What is an electrochemical gradient?

A

a difference in both the concentration of ions (chemical gradient) and the electric charge (electrical gradient) across a plasma membrane

103
Q

What is the concentration of Na+ and K+?

A

Na+ is more on the outside
K+ is more on the inside

104
Q

What are ion-channel-coupled receptors?

A

proteins that open in response to a signaling molecule

105
Q

How do ion-channel-coupled receptors behave in the absence of a signal?

A

usually closed until a signaling molecule is received

106
Q

What happens when an ion-channel-coupled receptor is activated?

A

Once open, the channels mediate passive transport, allowing ions to flow down their electrochemical gradient

107
Q

How can ion channels be gated by different signals?

A
  • voltage-gated
  • ligand-gated (extracellular ligand)
  • ligand-gated (intracellular ligand)
  • mechanically gated
108
Q

What is the state of synaptic vesicles in a resting synapse?

A

synaptic vesicles of neurotransmitters are waiting near the plasma membrane of the pre-synaptic cell

109
Q

What is the condition of ion channels in the target cell during a resting synapse?

A

Gated ion channels in the target cell are closed during a resting synapse

110
Q

What initiates the release of neurotransmitters in an active chemical synapse?

A

A nerve impulse causes neurotransmitter release by vesicle fusion to the plasma membrane

111
Q

What happens to neurotransmitters in the extracellular space during synaptic signaling?

A

open the ligand-gated ion channels in the target cell

112
Q

What occurs after ligand-gated ion channels open in the target cell?

A

Ions move into the target cell down their concentration gradient, triggering responses in the target cell

113
Q

What are G-Protein-Coupled Receptors (GPCRs)?

A

a large family of membrane receptors that mediate various signaling pathways in response to external signals

114
Q

How many GPCRs are present in humans?

A

over 800

115
Q

Why are GPCRs significant in pharmacology?

A

Almost half of all pharmaceuticals target GPCR pathways

116
Q

What types of signals can activate GPCRs?

A

small molecules, light, proteins, and more

117
Q

What is the structure of the heterotrimeric G-protein complex?

A

three subunits: Gα (alpha), Gβ (beta), and Gγ (gamma)

118
Q

How does an activated GPCR function as a GEF?

A
  • by facilitating the exchange of GDP for GTP on the Gα subunit
  • activates the GPCR
119
Q

What occurs after the dissociation of GTP-bound Gα from Gβγ?

A

both GTP-bound Gα and the Gβγ complex can activate different downstream signaling targets (they could both activate things)

120
Q

What happens to GTP-bound G⍺ over time?

A

The GTPase activity of G⍺ hydrolyzes GTP to GDP, thus inactivating the G⍺ subunit

121
Q

What is the function of the Regulator of G protein signaling (RGS)?

A

acts as a GAP to promote GTP hydrolysis by G⍺

122
Q

What occurs when G⍺ is bound to GDP?

A

re-associate with the Gβ𝛾 subunits of the heterotrimeric G-protein complex

123
Q

How do different G proteins activate signaling pathways?

A

by relying on various combinations of the Gα, Gβ, and Gγ subunits

124
Q

What is one common pathway that some G proteins signal through?

A

through adenylyl cyclase to produce cyclic AMP (cAMP)

125
Q

Besides adenylyl cyclase, what is another mechanism through which G proteins can signal?

A

activate phospholipase enzymes, which signal through lipids and calcium channels

126
Q

What is cAMP?

A

a small molecule secondary messenger

127
Q

What are the typical cellular concentrations of cAMP?

A

usually very low, but large amounts are produced in response to signals

128
Q

How is cAMP synthesized?

A

from ATP by the enzyme adenylyl cyclase

129
Q

What enzyme is responsible for breaking down cAMP?

A

cAMP phosphodiesterase

130
Q

What type of protein complex is activated by GPCRs?

A

heterotrimeric G-protein complex, specifically Gs

131
Q

What does GTP-bound G⍺ activate?

A

activates adenylyl cyclase

132
Q

What is the function of adenylyl cyclase?

A

converts ATP into cyclic AMP (cAMP)

133
Q

What is the structure of inactive protein kinase A (PKA)?

A

4 subunits
- 2 regulatory subunits
- 2 catalytic subunits

134
Q

How does cAMP activate protein kinase A (PKA)?

A
  • 2 molecules of cAMP bind to each regulatory subunit
  • catalytic subunits are released and are now active kinases
135
Q

What initiates Gs signaling?

A

The ligand binds and activates the GPCR

136
Q

What role does the activated GPCR play in Gs signaling?

A

acts as a GEF to exchange GDP for GTP on the G⍺ subunit of Gs

137
Q

What happens after GTP binds to G⍺?

A

activates adenylyl cyclase

138
Q

What is the function of adenylyl cyclase in Gs signaling?

A

converts ATP to cAMP (cyclic AMP)

139
Q

How does cAMP affect PKA (protein kinase A)?

A

binds to the regulatory subunits of PKA, releasing the catalytic domains from inhibition

140
Q

What occurs after PKA is activated?

A

moves to the nucleus

141
Q

What is the role of PKA in the nucleus?

A

phosphorylates CREB

142
Q

How does phosphorylated CREB contribute to gene expression?

A

binds to the CRE (cAMP-responsive element) along with CREB-binding protein to activate transcription of target genes

143
Q

What is the role of GPCRs in the human sense of smell?

A
  • recognizing different odorants
  • Humans have approximately 350 different GPCRs
  • each specific to a different odorant.
144
Q

How many GPCRs does each olfactory neuron express?

A

Each olfactory neuron expresses many copies of only one type of GPCR per neuron, located in the cilia

145
Q

What is the role of Golf in the olfactory signaling pathway?

A

Golf is activated by the GPCR and triggers the production of cAMP

146
Q

What does cAMP do in the context of olfactory signaling?

A

opens cAMP-gated cation channels

147
Q

What happens as a result of cation influx in olfactory neurons?

A

influx of cations triggers an action potential

148
Q

What type of G-protein complex is activated by GPCRs to signal through phospholipase C-β?

A

heterotrimeric G-protein complex Gq.

149
Q

What is the role of the GTP-bound G⍺ subunit in the signaling pathway involving phospholipase C-β?

A

activates phospholipase C-β

150
Q

What enzyme cleaves PI(4,5)P2 to produce diacylglycerol (DAG) and inositol trisphosphate (IP3)?

A

Phospholipase C-β (PLCβ)

151
Q

What are the two products generated from the cleavage of PI(4,5)P2 by PLCβ?

A

Diacylglycerol (DAG) and inositol trisphosphate (IP3).

152
Q

What is the role of diacylglycerol (DAG) in cell signaling?

A

diffuses in the membrane to activate protein kinase C (PKC)

153
Q

How does inositol trisphosphate (IP3) contribute to cellular signaling?

A

diffuses in the cytoplasm to open calcium (Ca2+) channels in the endoplasmic reticulum (ER)

154
Q

What type of molecules are DAG and IP3 classified as?

A

Small molecule secondary messengers

155
Q

What initiates the Gq signaling pathway?

A

A signal activates the G-protein-coupled receptor (GPCR

156
Q

What happens to the G-protein after the GPCR is activated?

A

activates the Gq protein, leading to the exchange of GDP for GTP on the Gα subunit, which then releases Gβγ

157
Q

What do GTP-Gα and Gβγ do in the Gq signaling pathway?

A

GTP-Gα activate phospholipase C-beta (PLCβ)

158
Q

What is the role of phospholipase C-beta (PLCβ) in Gq signaling?

A

cleaves phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) into two secondary messengers: diacylglycerol (DAG) and inositol trisphosphate (IP3).

159
Q

What is the function of inositol trisphosphate (IP3) in Gq signaling?

A

diffuses through the cytoplasm and opens gated calcium (Ca2+) channels in the endoplasmic reticulum

160
Q

What occurs when calcium (Ca2+) is released into the cytoplasm?

A

move into the cytoplasm

161
Q

How does diacylglycerol (DAG) function in the Gq signaling pathway?

A

DAG and Ca2+ activate protein kinase C (PKC)

162
Q

What is the role of protein kinase C (PKC) in the signaling pathway?

A

phosphorylates downstream targets

BIO230 Final (5 decks)

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