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Nuclear Transportation through NPCs

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Questions and Answers

What is the main function of the nuclear lamina?

To act as an anchoring site for chromosomes and nuclear pore complexes

What is the outer nuclear membrane continuous with?

The endoplasmic reticulum (ER)

What is the purpose of the nuclear pore complexes?

To conduct bidirectional traffic between the cytosol and the nucleus

Where are the ribosomes that synthesize proteins in the ER located?

<p>On the surface of the ER membrane</p> Signup and view all the answers

What is transported into the perinuclear space?

<p>Proteins synthesized in the ER</p> Signup and view all the answers

What are the proteins in the inner nuclear membrane part of?

<p>The nuclear lamina</p> Signup and view all the answers

What is the main function of the nuclear envelope?

<p>To separate the nucleus from the cytosol</p> Signup and view all the answers

What is the purpose of the protein complexes that span the nuclear envelope?

<p>To provide structural links between the DNA, nuclear envelope, and cytoskeleton</p> Signup and view all the answers

What is the primary function of a nuclear import receptor?

<p>To recognize and bind to nuclear localization signals</p> Signup and view all the answers

What happens to the nuclear localization signal on a cargo protein when it is loaded with a cargo protein?

<p>It becomes exposed</p> Signup and view all the answers

What is the role of adaptor proteins in nuclear import?

<p>To form a bridge between import receptors and nuclear localization signals</p> Signup and view all the answers

What is the function of the FG repeats in the unstructured domains of nucleoporins?

<p>To initially recruit import receptors and their bound cargo proteins to NPCs</p> Signup and view all the answers

What is the result of the import receptor binding to the FG repeats in the NPC pore?

<p>The receptor-–cargo complex locally dissolves the gel-like mesh and can diffuse into and within the NPC pore</p> Signup and view all the answers

What is the mechanism by which the import receptor accelerates cargo transport into the nucleus?

<p>Facilitated diffusion</p> Signup and view all the answers

What confers directionality to the nuclear import process?

<p>The selective dissociation of cargo only on the nuclear side of the NPC</p> Signup and view all the answers

What happens to the import receptor after it has transported cargo into the nucleus?

<p>It returns back to the cytosol for transport of the next cargo</p> Signup and view all the answers

What triggers the disassembly of the nuclear lamina during mitosis?

<p>Phosphorylation of the lamins</p> Signup and view all the answers

What is a common feature of the breakdown of the nuclear envelope during mitosis in metazoan cells?

<p>The lamina network breaks down</p> Signup and view all the answers

What occurs as decondensation of daughter chromosomes progresses?

<p>The membrane structures fuse</p> Signup and view all the answers

What is involved in the reassembly process of the nuclear envelope?

<p>Dephosphorylation of nucleoporins</p> Signup and view all the answers

In which organism does the nuclear envelope remain intact during mitosis?

<p>Yeast cells</p> Signup and view all the answers

What triggers the re-formation of the lamin network around the decondensing daughter chromosomes?

<p>Recruitment of membranes with interacting lamin receptors</p> Signup and view all the answers

In which cellular compartment is Ran GAP located?

<p>Cytosol</p> Signup and view all the answers

What happens to SREBP when the cholesterol-binding site on SCAP is empty?

<p>The SCAP-SREBP complex is packaged into transport vesicles</p> Signup and view all the answers

Where does the exchange of GDP for GTP occur to convert Ran-GDP to Ran-GTP?

<p>Nucleus</p> Signup and view all the answers

What is the result of SREBP binding to the promoters of genes involved in cholesterol biosynthesis?

<p>Activation of gene expression</p> Signup and view all the answers

What is the consequence of low cholesterol concentrations on SCAP?

<p>It changes conformation and dissociates from INSIG</p> Signup and view all the answers

Where is SREBP initially synthesized?

<p>Endoplasmic Reticulum</p> Signup and view all the answers

What is the purpose of the regulation of cholesterol biosynthesis through SREBP?

<p>To maintain a stable cholesterol concentration</p> Signup and view all the answers

What is the role of the SCAP-INSIG complex in cholesterol biosynthesis?

<p>It anchors SREBP in the ER when cholesterol levels are sufficient</p> Signup and view all the answers

What is the primary function of FG repeat–binding sites on the surface of nuclear import receptors?

<p>To rapidly partition into the FG repeat mesh</p> Signup and view all the answers

What is the result of the interaction between FG repeats and cargo receptors?

<p>The mesh is locally melted, accelerating diffusion through the NPC</p> Signup and view all the answers

What determines the directionality of nuclear import and export?

<p>The differential localization of Ran-GTP in the nucleus and Ran-GDP in the cytosol</p> Signup and view all the answers

What is the role of Ran GAP in the Ran GTPase cycle?

<p>To trigger the hydrolysis of GTP to produce Ran-GDP</p> Signup and view all the answers

What is the critical difference between Ran-mediated nuclear import and nuclear export?

<p>The nature of cargo binding by the cargo receptor</p> Signup and view all the answers

What is the characteristic of Ran GTPase?

<p>A molecular switch that can exist in two conformational states</p> Signup and view all the answers

What is the result of the interaction between cargo receptors and FG repeats in the NPC?

<p>The mesh is locally melted, accelerating diffusion through the NPC</p> Signup and view all the answers

What is the function of the mesh of FG repeat–containing proteins in the NPC?

<p>To restrict nonspecific diffusion of proteins and other macromolecules through the pore</p> Signup and view all the answers

Study Notes

The Nuclear Envelope

  • The nuclear envelope is a double membrane structure penetrated by nuclear pore complexes.
  • Transmembrane proteins in the inner and outer nuclear membranes link the nuclear lamina to the cytosolic cytoskeleton.
  • The outer nuclear membrane is continuous with the endoplasmic reticulum (ER).

The Lamina

  • The lamina provides structural support for the nuclear envelope and acts as an anchoring site for chromosomes and nuclear pore complexes.
  • The lamina is connected to the cytoplasmic cytoskeleton via protein complexes that span the nuclear envelope.

Nuclear Pore Complexes

  • Nuclear pores conduct extensive bidirectional traffic between the cytosol and the nucleus.
  • The many proteins that function in the nucleus are selectively imported into the nuclear compartment from the cytosol.
  • These proteins contain a nuclear localization signal that binds them to an import receptor.

Nuclear Import Receptors

  • Nuclear localization signals are recognized by nuclear transport receptors (karyopherin family members).
  • Each import receptor can bind and transport the subset of cargo proteins containing the appropriate nuclear localization signal.
  • Import receptors use adaptor proteins to form a bridge between the import receptors and the nuclear localization signals on the proteins to be transported.

Nuclear Import Mechanism

  • Import receptors contain multiple low-affinity binding sites for the FG repeats found in the unstructured domains of several nucleoporins.
  • The FG repeats in the fibrils of cytosol-facing nucleoporins serve to initially recruit import receptors and their bound cargo proteins to NPCs.
  • The import receptor-cargo complex diffuses into and within the NPC pore, allowing the cargo to traverse the distance across an NPC in a few milliseconds.

Ran GTPase Cycle

  • The Ran GTPase cycle provides directionality to both nuclear import and nuclear export.
  • The differential localization of Ran-GTP in the nucleus and Ran-GDP in the cytosol provides directionality.

Regulation of Nuclear Transport

  • Feedback regulation of cholesterol biosynthesis is an example of how transcription through NPCs can be regulated by controlling access to the transport machinery.
  • The breakdown and re-formation of the nuclear envelope and lamina occur during mitosis, with phosphorylation and dephosphorylation of the lamins triggering the disassembly and reassembly of the nuclear lamina.

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