Phosphoinositides as Regulators in Membrane Traffic

Camilli, Pietro De; Emr, Scott D.; McPherson, Peter S.; Novick, Peter

doi:10.1126/science.271.5255.1533

Cited by 693 publications

(481 citation statements)

References 107 publications

Supporting

Mentioning

469

Contrasting

Unclassified

Order By: Relevance

“…27 PI3K is a conserved family of lipid kinases that catalyze the phosphorylation of the position 3 of the inositol ring of phosphoinositides. [28][29][30] They produce lipids that are involved in cell proliferation, differentiation, apoptosis, autophagy, cytoskeletal organization, and membrane trafficking. Three classes of PI3K have been defined so far.…”

Section: Discussionmentioning

confidence: 99%

Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells

et al. 2004

View full text Add to dashboard Cite

Autophagy is originally named as a process of protein recycling. It begins with sequestering cytoplasmic organelles in a membrane vacuole called autophagosome. Autophagosomes then fuse with lysosomes, where the materials inside are degraded and recycled. To date, however, little is known about the role of autophagy in cancer therapy. In this study, we present that temozolomide (TMZ), a new alkylating agent, inhibited the viability of malignant glioma cells in a dose-dependent manner and induced G2/M arrest. At a clinically achievable dose (100 lM), TMZ induced autophagy, but not apoptosis in malignant glioma cells. After the treatment with TMZ, microtubule-associated protein lightchain 3 (LC3), a mammalian homologue of Apg8p/Aut7p essential for amino-acid starvation-induced autophagy in yeast, was recruited on autophagosome membranes. When autophagy was prevented at an early stage by 3-methyladenine, a phosphatidylinositol 3-phosphate kinase inhibitor, not only the characteristic pattern of LC3 localization, but also the antitumor effect of TMZ was suppressed. On the other hand, bafilomycin A1, a specific inhibitor of vacuolar type H þ -ATPase, that prevents autophagy at a late stage by inhibiting fusion between autophagosomes and lysosomes, sensitized tumor cells to TMZ by inducing apoptosis through activation of caspase-3 with mitochondrial and lysosomal membrane permeabilization, while LC3 localization pattern stayed the same. These results indicate that TMZ induces autophagy in malignant glioma cells. Application of an autophagy inhibitor that works after the association of LC3 with autophagosome membrane, such as bafilomycin A1, is expected to enhance the cytotoxicity of TMZ for malignant gliomas.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells

et al. 2004

View full text Add to dashboard Cite

show abstract

“…PIP 2 is a very important lipid in the cytoplasmic leaflet of the plasma membrane (De Camilli et al, 1996;Toker, 1998;Raucher et al, 2000;Martin, 2001;Payrastre et al, 2001;Cantley, 2002;Irvine, 2002;McLaughlin et al, 2002;Yin and Janmey, 2003) with a net charge of −4e on the lipid head group. By calculating the electrostatic free energy of laterally sequestering a PIP 2 lipid from a region of "bulk" membrane to a region in the vicinity of a membrane-absorbed basic peptide, Wang et al demonstrated that nonspecific electrostatic interactions provide a driving force for the lateral sequestration of PIP 2 by membrane-adsorbed basic peptides (Wang et al, 2001a;Rauch et al, 2002;Wang et al, 2004).…”

Section: Ivb Electrostatic Free Energymentioning

confidence: 99%

Computational Methods for Biomolecular Electrostatics

Dong

Olsen

Baker

2008

Biophysical Tools for Biologists, Volume One: In Vitro Techniques

116

View full text Add to dashboard Cite

An understanding of intermolecular interactions is essential for insight into how cells develop, operate, communicate and control their activities. Such interactions include several components: contributions from linear, angular, and torsional forces in covalent bonds, van der Waals forces, as well as electrostatics. Among the various components of molecular interactions, electrostatics are of special importance because of their long range and their influence on polar or charged molecules, including water, aqueous ions, and amino or nucleic acids, which are some of the primary components of living systems. Electrostatics, therefore, play important roles in determining the structure, motion and function of a wide range of biological molecules. This chapter presents a brief overview of electrostatic interactions in cellular systems with a particular focus on how computational tools can be used to investigate these types of interactions.

show abstract

“…Phosphoinositides are essential in several aspects of membrane traffic [9,10], and PITP has been found to be required. PITP is required for the exocytosis of secretory granules [11,12] and budding of secretory vesicles from the trans-Golgi network [13,14].…”

Section: Introductionmentioning

confidence: 99%

Purification and cloning of phosphatidylinositol transfer proteins from Dictyostelium discoideum: homologues of both mammalian PITPs and Saccharomyces cerevisiae Sec14p are found in the same cell

Swigart

Insall

Cockcroft

2000

Biochemical Journal

View full text Add to dashboard Cite

Soluble phosphatidylinositol transfer proteins (PITPs) have important roles in lipid-mediated signalling as well as in membrane traffic. Two PITPs (α and β) have been cloned from mammalian cells, which are unrelated in sequence to yeast PITP (the product of the SEC14 gene). However, all three PITPs can perform interchangeably to reconstitute function in mammalian cells. We have now purified the major PITP from the cytoplasm of Dictyostelium discoideum and cloned the gene. This protein, DdPITP1, is homologous with mammalian PITPα and PITPβ. We have also cloned a second gene (DdPITP2) related in sequence to DdPITP1. In addition, an independently cloned cDNA encodes a relative of the SEC14 family of yeast PITPs. DdPITP1, DdPITP2 and DdSec14 proteins were all able to mediate the transfer of PtdIns from one membrane compartment to another; they thus exhibited the hallmark of PITPs. Secondly, all three PITPs were able to rescue phospholipase C-mediated phosphoinositide hydrolysis in PITP-depleted HL60 cells, indicating that all three PITPs were capable of stimulating phosphoinositide synthesis. The identification of PITPs related to both mammalian PITPs and yeast Sec14p in a single organism will provide a unique opportunity to examine the functions of this class of protein with genetic approaches.

show abstract

Phosphoinositides as Regulators in Membrane Traffic

Cited by 693 publications

References 107 publications

Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells

Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells

Computational Methods for Biomolecular Electrostatics

Purification and cloning of phosphatidylinositol transfer proteins from Dictyostelium discoideum: homologues of both mammalian PITPs and Saccharomyces cerevisiae Sec14p are found in the same cell

Contact Info

Product

Resources

About