The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α

Journal article

Farnesylated prelamin A accumulates when the final endoproteolytic maturation of the protein fails to occur and causes a dysmorphic nuclear phenotype; however, the morphology and mechanisms of biogenesis of these changes remain unclear. We show here that acute prelamin A accumulation after reduction in the activity of the ZMPSTE24 endoprotease by short interfering RNA knockdown, results in the generation of a complex nucleoplasmic reticulum that depends for its formation on the enzyme CTP:phosphocholine-cytidylyltransferase-α (CCT-α, also known as choline-phosphate cytidylyltransferase A). This structure can form during interphase, confirming that it is independent of mitosis and therefore not a consequence of disordered nuclear envelope assembly. Serial-section dual-axis electron tomography reveals that these invaginations can take two forms: one in which the inner nuclear membrane infolds alone with an inter membrane space interior, and the other in which an invagination of both nuclear membranes occurs, enclosing a cytoplasmic core. Both types of invagination can co-exist in one nucleus and both are frequently studded with nuclear pore complexes (NPC), which reduces NPC abundance on the nuclear surface.

Authors: Goulbourne, C; Malhas, A; Vaux, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Company of Biologists
• Journal: Journal of Cell Science
• Volume: 124
• Issue: 24
• Pages: 4253-4266
• Publication date: 2011-12-01
• DOI: 10.1242/jcs.091009
• EISSN: 1477-9137
• ISSN: 0021-9533
• Language: English
• Keywords: nuclear lamina; electron tomography; nucleoplasmic reticulum