Phosphatidylinositol 5-phosphate

Phosphatidylinositol 5-phosphate (PtdIns5P) is a phosphoinositide, one of the phosphorylated derivatives of phosphatidylinositol (PtdIns), that are well-established membrane-anchored regulatory molecules. Phosphoinositides participate in signaling events that control cytoskeletal dynamics, intracellular membrane trafficking, cell proliferation and many other cellular functions. Generally, phosphoinositides transduce signals by recruiting specific phosphoinositide-binding proteins to intracellular membranes.[1]

Phosphatidylinositol 5-phosphate is one of the 7 known cellular phosphoinositides with less understood functions. It is phosphorylated on position D-5 of the inositol head group, which is attached via phosphodiester linkage to diacylglycerol (with varying chemical composition of the acyl chains, frequently 1-stearoyl-2-arachidonoyl chain). In quiescent cells, on average, PtdIns5P is of similar or higher abundance as compared to PtdIns3P and ~20-100-fold below the levels of PtdIns4P (Phosphatidylinositol 4-phosphate and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate).[2] Notably, steady-state PtdIns5P levels are more than 5-fold higher than those of PtdIns(3,5)P2.[3][4]

PtdIns5P was first demonstrated by HPLC (high pressure liquid chromatography) in mouse fibroblasts as a substrate for PtdIns(4,5)P2 synthesis by type II PIP kinases (1-phosphatidylinositol-5-phosphate 4-kinase).[5] In many cell types, however, PtdIns5P is not detected by HPLC due to technical limitations associated with its poor separation from the abundant PtdIns4P.[6] Rather, PtdIns5P is measured by the "mass assay", where PtdIns5P (as a part of the extracted cellular lipids) is converted in vitro by purified PtdIns5P 4-kinase to PtdIns(4,5)P2 that is subsequently quantified.[7]

Based on studies with the mass assay[6] and an improved HPLC technique,[8] PtdIns5P is detected in all studied mammalian cells. Most of the cellular PtdIns5P is found on cytoplasmic membranes whereas a smaller fraction resides in the nucleus.[9] The cytoplasmic and nuclear pools have distinct functions and regulation.[10]

  1. ^ Di Paolo, Gilbert; De Camilli, Pietro (2006-10-12). "Phosphoinositides in cell regulation and membrane dynamics". Nature. 443 (7112): 651–657. Bibcode:2006Natur.443..651D. doi:10.1038/nature05185. ISSN 1476-4687. PMID 17035995. S2CID 10479545.
  2. ^ Shisheva, Assia (2003-09-01). "Regulating Glut4 vesicle dynamics by phosphoinositide kinases and phosphoinositide phosphatases". Frontiers in Bioscience: A Journal and Virtual Library. 8 (6): s945–946. doi:10.2741/1101. ISSN 1093-9946. PMID 12957825.
  3. ^ Ikonomov, Ognian C.; Sbrissa, Diego; Delvecchio, Khortnal; et al. (2011-04-15). "The phosphoinositide kinase PIKfyve is vital in early embryonic development: preimplantation lethality of PIKfyve-/- embryos but normality of PIKfyve+/- mice". The Journal of Biological Chemistry. 286 (15): 13404–13413. doi:10.1074/jbc.M111.222364. ISSN 1083-351X. PMC 3075686. PMID 21349843.
  4. ^ Zhang, Yanling; Zolov, Sergey N.; Chow, Clement Y.; et al. (2007-10-30). "Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice". Proceedings of the National Academy of Sciences of the United States of America. 104 (44): 17518–17523. Bibcode:2007PNAS..10417518Z. doi:10.1073/pnas.0702275104. ISSN 0027-8424. PMC 2077288. PMID 17956977.
  5. ^ Rameh, L. E.; Tolias, K. F.; Duckworth, B. C.; Cantley, L. C. (1997-11-13). "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate". Nature. 390 (6656): 192–196. Bibcode:1997Natur.390..192R. doi:10.1038/36621. ISSN 0028-0836. PMID 9367159. S2CID 4403301.
  6. ^ a b Sbrissa, Diego; Ikonomov, Ognian C.; Deeb, Robert; Shisheva, Assia (2002-12-06). "Phosphatidylinositol 5-phosphate biosynthesis is linked to PIKfyve and is involved in osmotic response pathway in mammalian cells". The Journal of Biological Chemistry. 277 (49): 47276–47284. doi:10.1074/jbc.M207576200. ISSN 0021-9258. PMID 12270933.
  7. ^ Morris, J. B.; Hinchliffe, K. A.; Ciruela, A.; et al. (2000-06-09). "Thrombin stimulation of platelets causes an increase in phosphatidylinositol 5-phosphate revealed by mass assay". FEBS Letters. 475 (1): 57–60. Bibcode:2000FEBSL.475...57M. doi:10.1016/s0014-5793(00)01625-2. ISSN 0014-5793. PMID 10854858. S2CID 41475679.
  8. ^ Sarkes, Deborah; Rameh, Lucia E. (2010-05-27). "A novel HPLC-based approach makes possible the spatial characterization of cellular PtdIns5P and other phosphoinositides". The Biochemical Journal. 428 (3): 375–384. doi:10.1042/BJ20100129. ISSN 1470-8728. PMC 2944655. PMID 20370717.
  9. ^ Zou, Jun; Marjanovic, Jasna; Kisseleva, Marina V.; et al. (2007-10-23). "Type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase regulates stress-induced apoptosis". Proceedings of the National Academy of Sciences of the United States of America. 104 (43): 16834–16839. Bibcode:2007PNAS..10416834Z. doi:10.1073/pnas.0708189104. ISSN 0027-8424. PMC 2040409. PMID 17940011.
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