The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α.
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.
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE,  UK.
Chris N
CN
Goulbourne
Ashraf N
AN
Malhas
David J
DJ
Vaux
D000818:Animals; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D034904:Lamin Type A; D034921:Lamin Type B / Q000032:analysis; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D008938:Mitosis; D009685:Nuclear Envelope / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure*; D022022:Nuclear Pore / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D054876:Prenylation; D011498:Protein Precursors / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*
D034904:Lamin Type A; D034921:Lamin Type B; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A; D019916:Choline-Phosphate Cytidylyltransferase; C500611:Pcyt1a protein, mouse; D008666:Metalloendopeptidases; C491250:Zmpste24 protein, mouse