Multiple Aspects of PIP2 Involvement in C. elegans Gametogenesis

Abstract

One of the most studied phosphoinositides is phosphatidylinositol 4,5-bisphosphate (PIP2), which localizes to the plasma membrane, nuclear speckles, small foci in the nucleoplasm, and to the nucleolus in mammalian cells. Here, we show that PIP2 also localizes to the nucleus in prophase I, during the gametogenesis of C. elegans hermaphrodite. The depletion of PIP2 by type I PIP kinase (PPK-1) kinase RNA interference results in an altered chromosome structure and leads to various defects during meiotic progression. We observed a decreased brood size and aneuploidy in progeny, defects in synapsis, and crossover formation. The altered chromosome structure is reflected in the increased transcription activity of a tightly regulated process in prophase I. To elucidate the involvement of PIP2 in the processes during the C. elegans development, we identified the PIP2-binding partners, leucine-rich repeat (LRR-1) protein and proteasome subunit beta 4 (PBS-4), pointing to its involvement in the ubiquitin–proteasome pathway.

Lamin A/C and PI(4,5)P2—A Novel Complex in the Cell Nucleus

“…Another possible functional role of the lamin A/C—NM1—PI(4,5)P2 complex might be involvement in DNA damage response processes. Both PI(4,5)P2 [ 59 , 60 , 61 , 85 ] and NM1 [ 86 ] have been associated with DNA damage response. Hutchinson–Gilford Progeria syndrome (HGPS), which is characterized mostly by its accelerated normal human aging conditions [ 87 , 88 ], is caused by de novo mutations in the LMNA gene that activate an alternative pre-mRNA splice site leading to the expression of progerin—a lamin A mutant lacking 50 amino acids in its globular tail domain.…”

Nuclear Phosphoinositides—Versatile Regulators of Genome Functions

“…Furthermore, in Caenorhabditis elegans , depletion of PI(4,5)P2 results in chromosome structural changes which lead to various defects during meiotic progression. The altered chromosome structure is accompanied by the increased transcription activity, which might indicate the DNA-damage-driven apoptosis in the C. elegans gonad [115].…”