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Nucleocytoplasmic shuttling of phospholipase C‐δ 1 : A link to Ca 2+
Author(s) -
Yagisawa Hitoshi
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20677
Subject(s) - importin , nuclear transport , nuclear export signal , cytoplasm , microbiology and biotechnology , nuclear localization sequence , nucleus , cell nucleus , nls , ran , nuclear pore , chemistry , biology
Abstract Phosphoinositides (PIs) and proteins involved in the PI signaling pathway are distributed in the nucleus as well as at the plasma membrane and in the cytoplasm, although their nuclear localization mechanisms have not been clarified in detail. Generally, proteins that shuttle between the cytoplasm and nucleus contain nuclear localization signal (NLS) and nuclear export signal (NES) sequences for nuclear import and export, respectively. They bind to specific carrier proteins of the importin/exportin family and are transported to and from the nucleus. Thus there is a steady state shuttling of the cargo molecules to and from the nucleus, and the shift in equilibrium determines their nuclear or cytoplasmic localization. Our previous studies have shown that phospholipase C (PLC)‐δ 1 , regarded as having cytoplasmic‐ or plasma membrane‐bound localization, accumulates in the nucleus when its NES sequence is disrupted. In addition, a cluster of positively charged residues on the surface of the catalytic barrel is important for nuclear import. In quiescent cells, the shuttling equilibrium seems to be shifted to the nuclear export of PLCδ 1 . In this review, recent findings regarding the molecular machineries and mechanisms of the nucleocytoplasmic shuttling of PLCδ 1 will be discussed. It is important to know when and how they are regulated. A shift in the equilibrium in a certain stage of the cell cycle or by external stimuli is possible and resulting changes in the intra‐nuclear environments (or architectures) may alter proliferation and differentiation patterns. Evidences support the idea that an increase in the levels of intracellular Ca 2+ shifts the equilibrium to the nuclear import of PLCδ 1 . A myriad of external stimuli have also been reported to change the nuclear PI metabolism following accelerated accumulation in the nucleus of other phospholipases such as phospholipase A 2 and phospholipase D in addition to PLC isoforms such as PLCβ 1 and PLCγ 1 . The consequence of the nuclear accumulation of PLC is also discussed. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.