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Nucleocytoplasmic transport rates are regulated by cellular processes that modulate GTP availability
Kelsey L Scott1, Charles T Halfmann1, Allison D Hoefakker1,2
1Enabling Technologies Group, Sanford Research , Sioux Falls, SD, USA.
The Journal of Cell Biology
|April 29, 2024
Summary
Cellular physiology impacts nucleocytoplasmic transport (NCT) by altering GTP availability, which modulates the rate of cargo movement through nuclear pore complexes (NPCs). This regulation affects essential processes like RNA export and protein synthesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Nucleocytoplasmic transport (NCT) facilitates essential molecular exchange between the nucleus and cytoplasm via nuclear pore complexes (NPCs).
- Ran GTPase, utilizing GTP, establishes a gradient across the nuclear envelope (NE) to drive the majority of NCT.
Purpose of the Study:
- To investigate how altered cellular physiology affects GTP availability and consequently modulates NCT rates.
- To understand the relationship between cellular dynamics, GTP levels, Ran GTPase activity, and NCT.
Main Methods:
- Monitoring NCT rates using both synthetic and natural cargo molecules.
- Assessing the dynamics of Ran GTPase under varying physiological conditions.
- Correlating cellular processes like cell migration and cytoskeleton modulation with GTP availability and NCT rates.
Main Results:
- Changes in GTP availability, influenced by cellular physiology, directly alter the rate of NCT.
- Cell migration, cell spreading, and cytoskeleton dynamics were found to impact GTP availability.
- Modulated GTP availability affects Ran GTPase dynamics and regulates crucial cellular functions including RNA export and protein synthesis.
Conclusions:
- Cellular physiology plays a critical role in regulating NCT by modulating GTP availability.
- Altered GTP availability can fine-tune the rate of NCT, impacting fundamental cellular processes.
- This provides a mechanistic link between cellular state and the regulation of nuclear-cytoplasmic exchange.
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