scholarly journals Sec14-like phosphatidylinositol-transfer proteins and diversification of phosphoinositide signalling outcomes

2014 ◽  
Vol 42 (5) ◽  
pp. 1383-1388 ◽  
Author(s):  
Ashutosh Tripathi ◽  
Aaron H. Nile ◽  
Vytas A. Bankaitis
Keyword(s):  
Molecular Dynamics ◽  
Recent Work ◽  
Biological Activities ◽  
Model Organisms ◽  
Physiological Functions ◽  
Phosphatidylinositol Transfer ◽  
Phosphatidylinositol Transfer Proteins

The physiological functions of phosphatidylinositol (PtdIns)-transfer proteins (PITPs)/phosphatidylcholine (PtdCho)-transfer proteins are poorly characterized, even though these proteins are conserved throughout the eukaryotic kingdom. Much of the progress in elucidating PITP functions has come from exploitation of genetically tractable model organisms, but the mechanisms for how PITPs execute their biological activities remain unclear. Structural and molecular dynamics approaches are filling in the details for how these proteins actually work as molecules. In the present paper, we discuss our recent work with Sec14-like PITPs and describe how PITPs integrate diverse territories of the lipid metabolome with phosphoinositide signalling.

Phosphatidylinositol transfer proteins and protein kinase C make separate but non-interacting contributions to the phosphorylation state necessary for secretory competence in rat mast cells

2001 ◽  
Vol 356 (1) ◽  
pp. 287-296 ◽  
Author(s):  
Jef A. PINXTEREN ◽  
Bastien D. GOMPERTS ◽  
Danise ROGERS ◽  
Scott E. PHILLIPS ◽  
Peter E. R. TATHAM ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Aminoglycoside Antibiotic ◽  
Pleckstrin Homology Domain ◽  
Kinase C ◽  
Streptolysin O ◽  
Regulatory Machinery ◽  
Phosphatidylinositol Transfer ◽  
Phosphatidylinositol Transfer Proteins

Mast cells permeabilized by streptolysin O undergo exocytosis when stimulated with Ca2+ and guanosine 5′-[γ-thio]triphosphate but become progressively refractory to this stimulus if it is delayed. This run-down of responsiveness occurs over a period of 20–30min, during which the cells leak soluble and tethered proteins. We show here that withdrawal of ATP during the process of run-down is strongly inhibitory but that as little as 25μM ATP can extend responsiveness significantly; this effect is maximal at 50μM. When phosphatidylinositol transfer proteins (PITPs) are provided to cells at the time of permeabilization, run-down is retarded. We conclude that in the presence of ATP they convey substrates for phosphorylation that are essential for exocytosis and thus interact with the regulatory machinery. Furthermore, we show that PITPα and PITPβ have additive effects in this mechanism, suggesting that they are not functionally redundant. Alternatively, secretion from run-down cells can be inhibited by the aminoglycoside antibiotic neomycin, which is understood to bind to phosphoinositide headgroups, and by a PH (pleckstrin homology) domain polypeptide that binds phosphoinositides. The apparent displacement of neomycin by exogenous PITPs suggests that these proteins screen essential lipids. Secretion from run-down cells is also inhibited by 1-O-hexadecyl-2-O-methyl-rac-glycerol (AMG-C16), an inhibitor of protein kinase C. The lack of synergy between neomycin and AMG-C16 suggests that protein kinase C independently provides a second essential component through protein phosphorylation and that there are two independent phosphorylation pathways necessary for secretion competence.

Functional Analysis of Phosphatidylinositol Transfer Proteins

1996 ◽  
pp. 327-338 ◽  
Author(s):  
Brian G. Kearns ◽  
James G. Alb ◽  
Robert T. Cartee ◽  
Vytas A. Bankaitis
Keyword(s):  
Functional Analysis ◽  
Phosphatidylinositol Transfer ◽  
Phosphatidylinositol Transfer Proteins

Varying structural motifs in the salen based metal complexes of Co(ii), Ni(ii) and Cu(ii): synthesis, crystal structures, molecular dynamics and biological activities

2016 ◽  
Vol 45 (47) ◽  
pp. 19096-19108 ◽  
Author(s):  
Anoop Kumar Saini ◽  
Pratibha Kumari ◽  
Vinay Sharma ◽  
Pradeep Mathur ◽  
Shaikh M. Mobin
Keyword(s):  
Molecular Dynamics ◽  
Metal Complexes ◽  
Crystal Structures ◽  
Biological Activities ◽  
Biological Applications ◽  
Reaction Conditions ◽  
Structural Motifs

Four new metal complexes which demonstrates varying structural motifs from monomeric to dimeric to tetrameric complexes by slightly altering the reaction conditions and their biological applications.

scholarly journals 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

2000 ◽  
Vol 347 (3) ◽  
pp. 837-843 ◽  
Author(s):  
Philip SWIGART ◽  
Robert INSALL ◽  
Andrew WILKINS ◽  
Shamshad COCKCROFT
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Phospholipase C ◽  
Dictyostelium Discoideum ◽  
Mammalian Cells ◽  
Hl60 Cells ◽  
Single Organism ◽  
Membrane Compartment ◽  
Phosphatidylinositol Transfer ◽  
Cloned Cdna ◽  
Phosphatidylinositol Transfer Proteins

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.

scholarly journals Roco Proteins: GTPases with a Baroque Structure and Mechanism

2019 ◽  
Vol 20 (1) ◽  
pp. 147 ◽  
Author(s):  
Lina Wauters ◽  
Wim Versées ◽  
Arjan Kortholt
Keyword(s):  
Parkinson’S Disease ◽  
Recent Work ◽  
Protein Family ◽  
Leucine Rich Repeat ◽  
Working Mechanism ◽  
Ongoing Debate ◽  
Common Cause ◽  
Physiological Functions ◽  
Working Hypothesis ◽  
Domain Protein

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of genetically inherited Parkinson’s Disease (PD). LRRK2 is a large, multi-domain protein belonging to the Roco protein family, a family of GTPases characterized by a central RocCOR (Ras of complex proteins/C-terminal of Roc) domain tandem. Despite the progress in characterizing the GTPase function of Roco proteins, there is still an ongoing debate concerning the working mechanism of Roco proteins in general, and LRRK2 in particular. This review consists of two parts. First, an overview is given of the wide evolutionary range of Roco proteins, leading to a variety of physiological functions. The second part focusses on the GTPase function of the RocCOR domain tandem central to the action of all Roco proteins, and progress in the understanding of its structure and biochemistry is discussed and reviewed. Finally, based on the recent work of our and other labs, a new working hypothesis for the mechanism of Roco proteins is proposed.

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