Nuclear Phosphoinositides as Key Determinants of Nuclear Functions
Magdalena Castellano Vidalle, Bhavwanti Sheth, Antonietta Fazio, Maria Vittoria Marvi, Stefano Leto, Foteini‐Dionysia Koufi, Irene Neri, Irene Casalin, Giulia Ramazzotti, Matilde Y. Follo, Stefano Ratti, Lucia Manzoli, Sonakshi Gehlot, Nullin Divecha, Roberta Fiume
Abstract
Polyphosphoinositides (PPIns) are signalling messengers representing less than five per cent of the total phospholipid concentration within the cell. Despite their low concentration, these lipids are critical regulators of various cellular processes, including cell cycle, differentiation, gene transcription, apoptosis and motility. PPIns are generated by the phosphorylation of the inositol head group of phosphatidylinositol (PtdIns). Different pools of PPIns are found at distinct subcellular compartments, which are regulated by an array of kinases, phosphatases and phospholipases. Six of the seven PPIns species have been found in the nucleus, including the nuclear envelope, the nucleoplasm and the nucleolus. The identification and characterisation of PPIns interactor and effector proteins in the nucleus have led to increasing interest in the role of PPIns in nuclear signalling. However, the regulation and functions of PPIns in the nucleus are complex and are still being elucidated. This review summarises our current understanding of the localisation, biogenesis and physiological functions of the different PPIns species in the nucleus.