Karyopherin-βs play a key role as a phase separation regulator.

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• Cells use liquid-liquid phase separation (LLPS) to form membrane-less organelles like RNP granules.
• The nuclear pore complex (NPC) likely uses LLPS in its central channel for selective macromolecule transport.
• Aberrant LLPS of proteins, including intrinsically disordered regions (IDRs), is linked to neurodegenerative diseases.

Purpose of the Study:

• To review the role of Karyopherin-β proteins in regulating LLPS.
• To explore how Karyopherin-βs facilitate nuclear transport through the NPC.
• To understand the implications of Karyopherin-β-mediated LLPS regulation in health and disease.

Main Methods:

• Review of existing literature on LLPS, NPCs, and Karyopherin-β function.
• Analysis of the interactions between Karyopherin-βs and FG-nucleoporins.
• Examination of Karyopherin-β interactions with cargo proteins, including IDR-containing proteins.

Main Results:

• Karyopherin-β proteins dissolve phase-separated FG-nucleoporins in the NPC central channel.
• Karyopherin-βs also dissolve phase-separated cargo proteins.
• Weak interactions are crucial for Karyopherin-βs to mediate NPC passage and maintain cargo solubility.

Conclusions:

• Karyopherin-βs are key regulators of LLPS in nuclear transport.
• Their ability to dissolve phase-separated components is essential for NPC function.
• Understanding these mechanisms may offer insights into preventing diseases linked to aberrant LLPS.