Related Experiment Video
Updated: Jun 4, 2026
08:53
Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells
Published on: May 16, 2017
Nuclear pore complex during neuronal degeneration: cracking the last barrier!
Daniele Bano1, Michael O Hengartner, Pierluigi Nicotera
1Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany. daniele.bano@dzne.de
Nucleus (Austin, Tex.)
|February 18, 2011
Summary
Nuclear pore complex (NPC) degradation increases permeability during calcium-mediated neuronal degeneration. This nucleocytoplasmic transport alteration may contribute to neuronal demise, potentially preceding nuclear envelope breakdown.
Area of Science:
- Cell Biology
- Neuroscience
- Molecular Biology
Background:
- The Nuclear Pore Complex (NPC) regulates molecular transport between the nucleus and cytosol in eukaryotic cells.
- NPCs are crucial for cellular function, and their disruption is implicated in degenerative processes.
- Alterations in NPC composition and nucleocytoplasmic transport are linked to cellular stress and demise.
Purpose of the Study:
- To investigate the role of NPC alterations in calcium-mediated neuronal degeneration.
- To determine if NPC component degradation and increased permeability precede nuclear envelope disassembly.
- To explore the contribution of nucleocytoplasmic transport disruption to neuronal death.
Main Methods:
- The study focuses on analyzing changes in NPC components during calcium-mediated neuronal degeneration.
- Investigated the correlation between calcium overload and NPC degradation.
- Assessed the impact of NPC alterations on nuclear envelope permeability and nucleocytoplasmic transport.
Main Results:
- NPC components are degraded during calcium-mediated neuronal degeneration, leading to increased NPC channel permeability.
- These NPC changes occur earlier than the final disassembly of the nuclear envelope.
- Calcium overload was identified as a mediator of these NPC alterations.
Conclusions:
- Increased NPC leakiness, driven by nucleoporin loss and altered nucleocytoplasmic transport, may be a key event in excitotoxic neuronal death.
- NPC dysfunction could be an early executioner rather than a late consequence in neuronal demise.
- Further research is needed to fully elucidate the role of NPCs in neurodegeneration.
Related Concept Videos
01:34Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:26Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
02:31Nuclear Export of mRNA
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
01:42Nuclear Export
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
01:15Neurogenesis and Regeneration of Nervous Tissue
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...