Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Nuclear envelope (NE) assembly is essential for eukaryotic cell function.
• While the GTPase Ran is known to be involved, the specific membrane fusion machinery remains largely uncharacterized.
• NE assembly involves chromatin-associated network formation, fusion into a closed structure, and expansion.

Purpose of the Study:

• To elucidate the molecular mechanisms and machinery involved in nuclear envelope (NE) assembly.
• To identify the specific roles of the AAA-ATPase p97 and its adaptors in NE formation.
• To characterize the membrane fusion events critical for NE biogenesis.

Main Methods:

• Investigated the function of p97, an AAA-ATPase, and its associated proteins (p47, Ufd1, Npl4) in NE assembly.
• Utilized biochemical and cell biological approaches to dissect the distinct roles of p97 complexes.
• Focused on the processes of closed NE formation and subsequent NE growth.

Main Results:

• p97 has two distinct functions in NE assembly, mediated by different protein complexes.
• The p97-Ufd1-Npl4 complex is essential for the formation of a closed NE.
• A separate p97-p47 complex drives the subsequent growth and expansion of the NE.

Conclusions:

• This study provides the first detailed molecular insights into the fusion events governing NE formation.
• Identified specific AAA-ATPase complexes (p97-Ufd1-Npl4 and p97-p47) as key players in NE biogenesis.
• Characterized the distinct roles of p97 in both the initial closure and subsequent expansion of the nuclear envelope.