Caspases target only two architectural components within the core structure of the nuclear pore complex

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The nuclear pore complex (NPC) regulates transport between the nucleus and cytoplasm.
• NPCs are crucial for maintaining cellular function and are implicated in apoptosis.
• Caspases, key apoptotic proteases, are suspected to impair NPC function during programmed cell death.

Purpose of the Study:

• To investigate which nuclear pore proteins are targeted by caspases during apoptosis.
• To understand how caspases disrupt NPC function while preserving its overall structure.

Main Methods:

• Analysis of all known nuclear pore proteins during apoptosis.
• Identification of caspase cleavage sites on nuclear pore proteins.

Main Results:

• Only two NPC core components, Nup93 and Nup96, were identified as caspase targets.
• Cleavage occurs near the N-terminus, disrupting interaction domains essential for transport and barrier function.
• NPC scaffold integrity is maintained despite targeted proteolysis.

Conclusions:

• Caspase-mediated cleavage of Nup93 and Nup96 efficiently disables NPC function during apoptosis.
• This targeted proteolysis represents a strategy to rapidly impair large molecular machines.
• NPC structural integrity is largely preserved, indicating functional inactivation precedes gross morphological changes.