The Role of PIP2 in Actin, Actin-Binding Proteins and Disease
Phosphatidylinositol(4,5) bisphosphate (PI(4,5)P2 or more simply, PIP2 is only a minor component of the cell membrane lipids but it is the most abundant of the bisphorylated phosphoinositides. PIP2 is a key ligand in regulating the activity of a number of actin-binding proteins that regulate the assembly of actin microfilaments (Logan and Mandato 2006; Yin and Janmey 2003). Because of its central role, abnormal accumulation of PIP2 in the cell might be expected to produce defects in the assembly of cytoplasmic actin microfilaments. Similarly, a substantial reduction in cellular PIP2 is also not likely to be tolerated. Thus, mutations in enzymes that control cellular PIP2 content may be responsible, either directly or indirectly, for a number of human diseases/disorders.
KeywordsActin Cytoskeleton Actin Microfilament Glomerular Epithelial Cell Lowe Syndrome OCRL Mutation
Unable to display preview. Download preview PDF.
- Godi, A., Di Campli, A. and De Matteis, A. 2004. Phosphoinositides and membrane traffic in health and disease. Top. Curr. Genet. 10, 171-192.Google Scholar
- Gorbatyuk, V. Y., Nosworthy, N. J., Robson, S. A., Bains, N. P. S., Maciejewski, M. W., dos Remedios, C. G. and King, G. F. 2006. Mapping of a novel phosphoinositide binding site on chick cofilin explains how PIP2 regulated the cofilin-actin interaction. Mol. Cell 24, 511-522.CrossRefPubMedGoogle Scholar
- Lowe, C. U., Terrey, M. and MacLachan, E. A. 1952. Organic aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity. Am. J. Dis. Child. 83, 164-184.Google Scholar
- Mueller, O. Y., Hartsfield, J. K., Hughes, E., Crolla, J. A., Dubowitz, V. and Bobrow, M. 1985. A balanced de-novo X/autosome translocation in a girl with manifestation of Lowe syndrome. Am. J. Med. Genet. 23, 837-847.Google Scholar
- Nussbaum, R. L. and Suchy, S. F. 2001. The oculocerebrorenal syndrome of Lowe (Lowe syndrome). In Metabolic and Molecular Basis of Inherited Disease, vol. 252, 8th edition. C. R. Scriver, A. L. Beaudet, W. S. Sly and D. Valle (Editors). McGraw-Hill, New York. pp. 6257-6266.Google Scholar