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Y1 Cellular Biochemistry and Biology > L16: Moving Into The Nucleus > Flashcards

L16: Moving Into The Nucleus Flashcards

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1
Q

What is the defining feature of a eukaryotic cell?

A

The membrane-bound nucleus.

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2
Q

What is the role of lysosomes in the cell?

A

They enable protein turnover through a low pH environment for protein unfolding and degradation.

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3
Q

Why is compartmentalisation important in eukaryotic cells?

A

It allows distinct environments for specialised functions, protects the local environment, and regulates interactions and cellular processes.

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4
Q

Name three mechanisms of molecular exchange between cellular compartments.

A

Gated transport, transmembrane transport, and vesicular transport.

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5
Q

What is the function of the nuclear pore complex (NPC)?

A

It enables the gated transport of proteins and molecules between the cytoplasm and the nucleus.

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6
Q

What are FG-Nups, and what is their role in the NPC?

A

FG-Nups are intrinsically disordered proteins with phenylalanine-glycine repeats that form a hydrogel, acting as a selective barrier within the NPC.

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7
Q

What happens in the genetic disease progeria regarding Lamin A processing?

A

Mutations prevent the final cleavage of prelamin A, causing defective nuclear architecture and DNA damage.

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8
Q

How does mislocalisation of proteins lead to disease?

A

For example, mutations in ATP7B, a copper metabolism protein, can lead to toxic copper buildup, causing liver and neurological damage.

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9
Q

What is the structural organisation of the nuclear envelope?

A

It consists of an inner and outer phospholipid bilayer, supported by the nuclear lamina.

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10
Q

Describe the nuclear lamina and its function.

A

It is a network of filaments made of Lamin proteins (A, B, and C) that provide structural support to the nuclear envelope and aid in DNA replication and regulation.

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11
Q

What is the significance of the nuclear localisation sequence (NLS)?

A

It is an amino acid sequence required for the translocation of transcription factors and other proteins into the nucleus.

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12
Q

What is unique about the nucleus in eukaryotic cells?

A

It separates gene expression (in the nucleus) from mRNA translation (in the cytoplasm), allowing precise regulation.

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13
Q

How does vesicular transport contribute to cellular processes?

A

It enables protein and molecule transport via membrane fusion, such as in secretion and endocytosis.

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14
Q

What are the three main types of nucleoporins (Nups) in the nuclear pore complex?

A

Core scaffolding Nups (outer, inner, and transmembrane), FG-Nups, and linker Nups.

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15
Q

How is the hydrogel barrier in the NPC formed?

A

By weak interactions between phenylalanine residues in FG-Nups, creating a selective barrier for molecular transport.

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16
Q

What are the two types of chromatin seen in the nucleus, and what do they signify?

A

Heterochromatin (dark, silenced genes) and euchromatin (light, active genes).

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17
Q

What is the nuclear envelope, and how is it related to the endoplasmic reticulum?

A

The nuclear envelope is a double phospholipid bilayer continuous with the endoplasmic reticulum.

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18
Q

What is the primary function of the nucleolus?

A

It is essential for ribosome biogenesis.

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19
Q

What happens to the nuclear pore complex during the cell cycle?

A

It is dismantled and rebuilt with each cell cycle as the nuclear envelope breaks down and reforms.

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20
Q

What is the approximate size and transport capacity of the nuclear pore complex?

A

It has a diameter of 35 nanometres and can transport up to 16 proteins per second.

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21
Q

How does the mutation in the nuclear localisation sequence (NLS) affect Swyer Syndrome?

A

It prevents the transcription factor SRY from entering the nucleus, disrupting male sex development.

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22
Q

Why is oxidative stress contained within mitochondria?

A

To prevent reactive oxygen species (ROS) from damaging other cellular components.

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23
Q

What is the significance of laminin A processing?

A

Proper processing ensures nuclear envelope integrity and prevents diseases like progeria.

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24
Q

How do neurons exemplify the importance of compartmentalisation?

A

Gene expression occurs in the nucleus, but proteins must be transported to synapses for their function.

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25
Q

What is the role of motor proteins in intracellular transport?

A

They move vesicles along the cytoskeleton to specific cellular destinations.

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26
Q

Why is the production of reactive oxygen species (ROS) tightly regulated?

A

Excess ROS can cause cellular damage if not metabolised into less toxic compounds.

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27
Q

What is the role of signal peptides in protein secretion?

A

They direct proteins to the endoplasmic reticulum for secretion or membrane integration.

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28
Q

What structural feature of the NPC facilitates its symmetric design?

A

The eightfold symmetry of its core structure.

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29
Q

What does the ‘phenylalanine-glycine (FG)’ motif in FG-Nups enable?

A

The formation of hydrogels that selectively filter nuclear transport.

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30
Q

How do vesicles contribute to endocytosis?

A

By allowing the uptake of extracellular molecules into the cell through membrane fusion.

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31
Q

What cellular problem arises from the mislocalisation of AVP2?

A

It leads to dehydration due to impaired water regulation in cells.

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32
Q

What is the importance of compartmentalisation in eukaryotic cells?

A

It enables control of interactions, regulation of local environments, specialisation of cellular functions, and protection from toxic metabolites.

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33
Q

How does the low pH of lysosomes benefit cellular processes?

A

It enables protein unfolding and degradation while preventing damage to other parts of the cell.

34
Q

What are the three main types of transport mechanisms across cellular compartments?

A

Gated transport (e.g., nuclear-cytoplasmic exchange), transmembrane transport (e.g., protein folding through membranes), and vesicular transport (e.g., endocytosis and exocytosis).

35
Q

What happens when ATP7B, a protein responsible for copper metabolism, is mislocalised?

A

It causes copper buildup, leading to liver failure and neurological problems.

36
Q

Why is the NPC referred to as a ‘molecular sieve’?

A

It allows passive diffusion of small molecules while controlling the active, gated transport of larger proteins.

37
Q

What is the role of Lamin proteins in the nuclear lamina?

A

They provide structural support to the nucleus, assist in DNA replication, and regulate gene expression.

38
Q

What is the function of phenylalanine in FG-Nups within the NPC?

A

Its aromatic properties create weak interactions that form the hydrogel barrier for selective transport.

39
Q

How does the uncoupling of gene expression and mRNA translation benefit eukaryotic cells?

A

It allows precise regulation and coordination of these processes.

40
Q

Why is the processing of prelamin A important for nuclear structure?

A

Proper processing ensures nuclear envelope stability and prevents diseases like progeria, where defective processing disrupts nuclear architecture.

41
Q

How does vesicular transport maintain cellular communication?

A

By enabling the movement of molecules and proteins between cellular compartments or into and out of the cell.

42
Q

Describe the structural complexity of the nuclear pore complex (NPC).

A

The NPC is the largest protein complex in the cell, comprising over 500 proteins organised in an eightfold symmetric structure.

43
Q

What structural feature of FG-Nups makes them flexible and functional in the NPC?

A

Their intrinsically disordered nature with interspaced phenylalanine-glycine motifs.

44
Q

What is the consequence of mutating phenylalanine in FG-Nups to serine?

A

It disrupts the hydrogel barrier, making the nuclear pore overly porous.

45
Q

What are some diseases caused by mislocalisation of transcription factors?

A

Disorders like Swyer syndrome, where mutations prevent proper nuclear localisation and disrupt gene expression.

46
Q

Why does the nuclear pore complex need to be rebuilt during the cell cycle?

A

It is dismantled as the nuclear envelope breaks down during mitosis and must be reassembled afterward to resume nuclear transport.

47
Q

What enables rapid delivery of prelamin A to the nuclear envelope?

A

Farnesylation of the C-terminal motif, which aids in targeting and initial localisation before further processing.

48
Q

How do mutations in the nuclear localisation sequence (NLS) affect proteins?

A

They prevent proteins from entering the nucleus, impacting processes like gene regulation and contributing to diseases.

49
Q

Why is the nucleus considered the ‘command centre’ of the cell?

A

It houses genetic material, regulates gene expression, and coordinates cellular functions through communication with the cytoplasm.

50
Q

What is the function of the nuclear lamina’s Lamin-associated proteins?

A

They tether Lamins to the inner nuclear membrane and aid in nuclear structural stability and gene regulation.

51
Q

How do oxidative phosphorylation and ROS production in mitochondria exemplify compartmentalisation?

A

Reactive oxygen species (ROS) are confined and detoxified within mitochondria, preventing damage to other cellular regions.

52
Q

How does the NPC facilitate energy-dependent transport?

A

The NPC uses gradients (e.g., Ran-GTP/GDP) and interactions with specific transport receptors (importins/exportins) to drive energy-dependent transport.

53
Q

How does the FG hydrogel in the nuclear pore complex influence movement?

A

The FG hydrogel does not direct movement but allows random diffusion, guided by the Ran-GTP gradient to promote transport directionality.

54
Q

What is the role of phosphorylation adjacent to the NLS in SV40 Large T antigen?

A

Phosphorylation adjacent to the NLS increases recognition by importin alpha, enhancing nuclear import.

55
Q

What happens to importins after releasing their cargo in the nucleus?

A

Importins are recycled back to the cytoplasm to pick up new cargo, driven by the Ran-GTP/GDP gradient.

56
Q

Why is the nuclear pore complex important for messenger RNA (mRNA) export quality control?

A

The NPC ensures only properly spliced and processed mRNAs are exported, preventing defective mRNA from entering the cytoplasm.

57
Q

How can a single amino acid substitution mimic phosphorylation?

A

Replacing serine with aspartic acid mimics a phosphate group, allowing the protein to behave as if it were phosphorylated.

58
Q

What defines the direction of protein movement through the NPC?

A

The Ran-GTP gradient, with high Ran-GTP in the nucleus and high Ran-GDP in the cytoplasm, drives directionality.

59
Q

How do exportins work in nuclear export?

A

Exportins bind cargo and Ran-GTP in the nucleus, move through the NPC, and release cargo in the cytoplasm when Ran-GTP is hydrolysed to Ran-GDP.

60
Q

What is the function of the protein NFX1 in mRNA export?

A

NFX1 recognises the 3’ cap of mature mRNA and facilitates its localisation to the nuclear pore complex for export.

61
Q

How does a conformational change induced by phosphorylation regulate nuclear import?

A

Phosphorylation can expose or hide the NLS, altering recognition by importins and thus controlling nuclear import.

62
Q

What is the role of Gle1 and DDX19 in mRNA export?

A

These proteins create a cytoplasmic gradient that facilitates mRNA movement out of the nucleus without relying on Ran-GTP.

63
Q

How does phosphorylation regulate NFAT localisation?

A

Phosphorylation of NFAT retains it in the cytoplasm, while dephosphorylation by calcineurin allows nuclear import during T-cell activation.

64
Q

Why do importins alpha and beta work as a team?

A

Importin alpha binds the cargo’s NLS, and importin beta interacts with FG nucleoporins, enabling coordinated transport through the NPC.

65
Q

What is the role of RanGEF and where is it located?

A

RanGEF is a nucleus-localised protein that loads GTP onto Ran, maintaining high levels of Ran-GTP in the nucleus.

66
Q

What happens to Ran-GTP once it reaches the cytoplasm?

A

Ran-GTP is hydrolysed to Ran-GDP by RanGAP, maintaining the cytoplasmic Ran-GDP gradient.

67
Q

How is the NPC structured to enable selective transport?

A

The NPC contains FG nucleoporins forming a selective barrier, recognising transport receptors like importins and exportins.

68
Q

What determines the high concentration of Ran-GTP in the nucleus?

A

RanGEF, a protein tethered to chromatin in the nucleus, facilitates the conversion of Ran-GDP to Ran-GTP, maintaining high nuclear levels of Ran-GTP.

69
Q

How does the phosphorylation of proteins influence nuclear export?

A

Phosphorylation can alter the nuclear export sequence (NES), either enhancing or inhibiting the recognition by exportins.

70
Q

Why is the localisation of RanGAP crucial for maintaining the Ran-GTP gradient?

A

RanGAP is localised on the cytoplasmic filaments of the NPC, where it hydrolyses Ran-GTP to Ran-GDP, sustaining the cytoplasmic Ran-GDP levels.

71
Q

What happens during the export of proteins via exportins?

A

Exportins bind cargo and Ran-GTP in the nucleus, translocate them through the NPC, and release cargo in the cytoplasm after Ran-GTP hydrolysis.

72
Q

How does the NPC recognise mRNA for export?

A

The NPC uses export proteins like NXF1, which bind to processed mRNA at its 3’ cap to guide it to the pore for export.

73
Q

What is the role of the NPC in quality control of mRNA export?

A

The NPC ensures mRNA is fully processed, including capping, splicing, and 3’ end formation, before allowing export to the cytoplasm.

74
Q

What type of amino acid sequence is commonly found in Nuclear Export Sequences (NES)?

A

NES are typically rich in leucine residues, which are recognised by exportins for nuclear export.

75
Q

How does phosphorylation influence the viral protein SV40 Large T antigen?

A

Phosphorylation near its NLS enhances recognition by importin alpha, significantly increasing nuclear import efficiency.

76
Q

What is the relationship between Ran-GTP hydrolysis and nuclear export?

A

Hydrolysis of Ran-GTP to Ran-GDP in the cytoplasm releases exportins and cargo, completing the export cycle.

77
Q

How does calcineurin regulate NFAT nuclear import?

A

Calcineurin dephosphorylates NFAT in response to high calcium levels, exposing the NLS and enabling nuclear import.

78
Q

Why is RanGAP located on the cytoplasmic side of the NPC?

A

Its location ensures the hydrolysis of Ran-GTP to Ran-GDP occurs as transport components exit the nucleus, sustaining the gradient.

79
Q

What is the purpose of the basket-like structure at the NPC?

A

The basket helps position mature mRNAs for export by interacting with export factors like TPR and NXF1.

80
Q

How is the hydrogel-like environment of the NPC maintained?

A

FG nucleoporins create a selective hydrogel that allows transport proteins to dock while restricting passive diffusion of larger molecules.

81
Q

What is the role of Gle1 in mRNA export?

A

Gle1 works with DDX19 at the cytoplasmic filaments of the NPC to create a gradient that facilitates mRNA export without Ran-GTP.

82
Q

How do mutations in the NLS affect protein localisation?

A

Mutations in the NLS can prevent proteins from entering the nucleus, causing them to remain in the cytoplasm.

Y1 Cellular Biochemistry and Biology (16 decks)

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