Evidence for Ca2+- and ATP-sensitive peripheral channels in nuclear pore complexes

Area of Science:

• Cell biology
• Biophysics

Background:

• The nuclear envelope (NE) regulates transport between the nucleus and cytoplasm via nuclear pore complexes (NPCs).
• While large central channels are known, peripheral NPC structures suggest alternative transport routes.
• The function of these peripheral structures and their role in transport remain unclear.

Purpose of the Study:

• To investigate the function of peripheral NPC structures in passive ion transport.
• To determine the role of calcium (Ca2+) and adenosine triphosphate (ATP) in regulating NE electrical conductance and transport.
• To differentiate ion and macromolecule transport pathways through NPCs.

Main Methods:

• Utilized the nuclear hourglass technique to measure NE electrical conductance.
• Manipulated cytosolic Ca2+ and ATP levels, and chelated Ca2+ in perinuclear stores in isolated Xenopus laevis oocyte nuclei.
• Employed atomic force microscopy to image native NPCs and detect peripheral pores.

Main Results:

• NE electrical conductance was high when macromolecule permeability was low.
• Atomic force microscopy revealed small peripheral pores in NPCs, detectable only with ATP.
• Ca2+ and ATP were identified as key regulators of passive ion transport.

Conclusions:

• NPCs utilize distinct routes for ion and macromolecule transport.
• Peripheral NPC channels, activated by Ca2+ and ATP, mediate NE ion flux.
• The central NPC channel is not the primary route for passive ion transport.