D5 dopamine receptors are required for dopaminergic activation of phospholipase C.

Dopamine activates phospholipase C in discrete regions of the mammalian brain, and this action is believed to be mediated through a D(1)-like receptor. Although multiple lines of evidence exclude a role for the D(1) subtype of D(1)-like receptors in the phosphoinositide response, the D(5) subtype has not been similarly examined. Here, mice lacking D(5) dopamine receptors were tested for dopamine agonist-induced phosphoinositide signaling both in vitro and in vivo.

Trans-Golgi network and endosome dynamics connect ceramide homeostasis with regulation of the unfolded protein response and TOR signaling in yeast.

Synthetic genetic array analyses identify powerful genetic interactions between a thermosensitive allele (sec14-1(ts)) of the structural gene for the major yeast phosphatidylinositol transfer protein (SEC14) and a structural gene deletion allele (tlg2Delta) for the Tlg2 target membrane-soluble N-ethylmaleimide-sensitive factor attachment protein receptor. The data further demonstrate Sec14 is required for proper trans-Golgi network (TGN)/endosomal dynamics in yeast. Paradoxically, combinatorial depletion of Sec14 and Tlg2 activities elicits trafficking defects from the endoplasmic reticulum, and these defects are accompanied by compromise of the unfolded protein response (UPR).

Functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the sec14 superfamily.

Sec14, the major yeast phosphatidylinositol (PtdIns)/phosphatidylcholine (PtdCho) transfer protein, regulates essential interfaces between lipid metabolism and membrane trafficking from the trans-Golgi network (TGN). How Sec14 does so remains unclear. We report that Sec14 binds PtdIns and PtdCho at distinct (but overlapping) sites, and both PtdIns- and PtdCho-binding activities are essential Sec14 activities.

Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain.

Background: Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action.

The Sec14-superfamily and the regulatory interface between phospholipid metabolism and membrane trafficking.

A central principle of signal transduction is the appropriate control of the process so that relevant signals can be detected with fine spatial and temporal resolution. In the case of lipid-mediated signaling, organization and metabolism of specific lipid mediators is an important aspect of such control. Herein, we review the emerging evidence regarding the roles of Sec14-like phosphatidylinositol transfer proteins (PITPs) in the action of intracellular signaling networks; particularly as these relate to membrane trafficking.

Tandem regulation of phosphoinositide signaling and acute behavioral effects induced by antidepressant agents in rats.

Rationale: Antidepressants increase synaptic monoamine concentrations, but the subsequent signaling events that produce the beneficial clinical effects remain unclear. Diverse antidepressants increase CDP-diacylglycerol, a crucial step in phosphoinositide signaling. Serotonin 5HT(2) receptors, implicated in depression or the actions of some antidepressants, signal through phosphoinositide hydrolysis.

Nonclassical PITPs activate PLD via the Stt4p PtdIns-4-kinase and modulate function of late stages of exocytosis in vegetative yeast.

Phospholipase D (PLD) is a PtdCho-hydrolyzing enzyme that plays central signaling functions in eukaryotic cells. We previously demonstrated that action of a set of four nonclassical and membrane-associated Sec14p-like phosphatidylinositol transfer proteins (PITPs) is required for optimal activation of yeast PLD in vegetative cells. Herein, we focus on mechanisms of Sfh2p and Sfh5p function in this regulatory circuit.