Control of diverse subcellular processes by a single multi-functional lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]

Abstract

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a multi-functional lipid that regulates several essential subcellular processes in eukaryotic cells. In addition to its well-established function as a substrate for receptor-activated signalling at the plasma membrane (PM), it is now recognized that distinct PI(4,5)P2 pools are present at other organelle membranes. However, a long-standing question that remains unresolved is the mechanism by which a single lipid species, with an invariant functional head group, delivers numerous functions without loss of fidelity. In the present review, we summarize studies that have examined the molecular processes that shape the repertoire of PI(4,5)P2 pools in diverse eukaryotes. Collectively, these studies indicate a conserved role for lipid kinase isoforms in generating functionally distinct pools of PI(4,5)P2 in diverse metazoan species. The sophistication underlying the regulation of multiple functions by PI(4,5)P2 is also shaped by mechanisms that regulate its availability to enzymes involved in its metabolism as well as molecular processes that control its diffusion at nanoscales in the PM. Collectively, these mechanisms ensure the specificity of PI(4,5)P2 mediated signalling at eukaryotic membranes.

Targeted Esterase induced Dye loading supports Calcium Imaging in Eukaryotic Cell-Free Systems

“…The concentration for activation and inhibition of hTRPV1 in our experiments are coherent with the molar range as the cell-based expression (45). Presence of Phosphatidylinositol 4,5-bisphosphate, (4,5)PIP 2 for activation of TRP channels has been debated by several researchers (46,47,48). In our work, we have shown that without external (4,5)PIP 2 , activation of TRPV1 was feasible.…”

“…In our work, we have shown that without external (4,5)PIP 2 , activation of TRPV1 was feasible. On the other hand, the phenomenon we observe can be supported by the presence of (4,5)PIP 2 in the endoplasmic reticulum and in the cytosol (48,49,50).…”

K-Ras G-domain binding with signaling lipid phosphoinositides: PIP2 association, orientation, function

“…In the context of cancer, phosphoinositides were shown to be major regulators of cell motility, invasion, and metastasis [Yamaguchi et al, 2010; Gagliardi et al, 2015; Lien et al, 2017]. Recent studies revealed, several classes of transmembrane receptors and ion channels might be regulated by PIP2, or at least bind this signaling lipid with considerable affinity [Hedger et al, 2015;Kolay et al, 2016, Chadli et al, 2017. Thus, PIP2 signaling may results in a cell-global concerted response to environmental changes.…”

Arabidopsis PCaP2 modulates the phosphatidylinositol 4,5‐bisphosphate signal on the plasma membrane and attenuates root hair elongation

“…Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2 ] is one of the best-studied signaling lipid in eukaryotes (Sun et al, 2013;Kolay et al, 2016). PtdIns(4,5)P 2 , as with other phosphoinositides, is localized to specific membranes or membrane subdomains (Krauss and Haucke, 2007;van Meer et al, 2008;Sasaki et al, 2009;Choi et al, 2015), allowing it to serve as an intracellular site-specific signal (Di Paolo and De Camilli, 2006;Shewan et al, 2011;Balla, 2013;Schink et al, 2016).…”