A budding yeast-centric view of oxysterol binding protein family function.

The Trans Golgi Network (TGN)/endosomal system is a sorting center for cargo brought via the anterograde secretory pathway and the endocytic pathway that internalizes material from the plasma membrane. As many of the cargo that transit this central trafficking hub are components of key homeostatic signaling pathways, TGN/endosomes define a critical signaling hub for cellular growth control. A particularly interesting yet incompletely understood aspect of regulation of TGN/endosome function is control of this system by two families of lipid exchange/lipid transfer proteins.

Regulatory insight for a Zn2Cys6 transcription factor controlling effector-mediated virulence in a fungal pathogen of wheat.

The regulation of virulence in plant-pathogenic fungi has emerged as a key area of importance underlying host infections. Recent work has highlighted individual transcription factors (TFs) that serve important roles. A prominent example is PnPf2, a member of the Zn2Cys6 family of fungal TFs, which controls the expression of effectors and other virulence-associated genes in Parastagonospora nodorum during infection of wheat.

Diverse Sphingolipid Species Harbor Different Effects on Ire1 Clustering.

Endoplasmic reticulum (ER) function is dedicated to multiple essential processes in eukaryotes, including the processing of secretory proteins and the biogenesis of most membrane lipids. These roles implicate a heavy burden to the organelle, and it is thus prone to fluctuations in the homeostasis of molecules which govern these processes. The unfolded protein response (UPR) is a general ER stress response tasked with maintaining the ER for optimal function, mediated by the master activator Ire1.

Cancer associated mutations in Sec61γ alter the permeability of the ER translocase.

Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the Sec61 complex, a heterotrimeric protein complex possessing two essential sub-units, Sec61p/Sec61α and Sss1p/Sec61γ and the non-essential Sbh1p/Sec61β subunit. In addition to forming a protein conducting channel, the Sec61 complex maintains the ER permeability barrier, preventing flow of molecules and ions. Loss of Sec61 integrity is detrimental and implicated in the progression of disease.

The conserved C-terminus of Sss1p is required to maintain the endoplasmic reticulum permeability barrier.

The endoplasmic reticulum (ER) is the entry point to the secretory pathway and major site of protein biogenesis. Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the evolutionarily conserved Sec61 complex, a heterotrimeric channel that comprises the Sec61p/Sec61α, Sss1p/Sec61γ, and Sbh1p/Sec61β subunits. In addition to forming a protein-conducting channel, the Sec61 complex also functions to maintain the ER permeability barrier, preventing the mass free flow of essential ER-enriched molecules and ions.

Functional diversification of the chemical landscapes of yeast Sec14-like phosphatidylinositol transfer protein lipid-binding cavities.

Phosphatidylinositol-transfer proteins (PITPs) are key regulators of lipid signaling in eukaryotic cells. These proteins both potentiate the activities of phosphatidylinositol (PtdIns) 4-OH kinases and help channel production of specific pools of phosphatidylinositol 4-phosphate (PtdIns(4)P) dedicated to specific biological outcomes. In this manner, PITPs represent a major contributor to the mechanisms by which the biological outcomes of phosphoinositide are diversified.

An equal opportunity collaboration between lipid metabolism and proteins in the control of membrane trafficking in the trans-Golgi and endosomal systems.

Recent years have witnessed the evolution of the cell biology of lipids into an extremely active area of investigation. Deciphering the involvement of lipid metabolism and lipid signaling in membrane trafficking pathways defines a major nexus of contemporary experimental activity on this front. Significant effort in that direction is invested in understanding the trans-Golgi network/endosomal system where unambiguous connections between membrane trafficking and inositol lipid and phosphatidylcholine metabolism were first discovered.

WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins.

This article has been withdrawn by the authors as part of this review overlapped with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular Life Sciences.

The Impact of Cooling Rate on the Safety of Food Products as Affected by Food Containers.

In recent decades, the demand for ready-to-eat (RTE) food items prepared by the food catering sector has increased together with the value of cook-serve, cook-chill, and cook-freeze food products. The technologies by which foods are cooked, chilled, refrigerated for storage, and reheated before serving are of prime importance to maintain safety. Packaging materials and food containers play an important role in influencing the cooling rate of RTE foods.

Diminished Ost3-dependent N-glycosylation of the BiP nucleotide exchange factor Sil1 is an adaptive response to reductive ER stress.

BiP (Kar2 in yeast) is an essential Hsp70 chaperone and master regulator of endoplasmic reticulum (ER) function. BiP's activity is regulated by its intrinsic ATPase activity that can be stimulated by two different nucleotide exchange factors, Sil1 and Lhs1. Both Sil1 and Lhs1 are glycoproteins, but how N-glycosylation regulates their function is not known.

Lipid transfer proteins and the tuning of compartmental identity in the Golgi apparatus.

The Golgi complex constitutes a central way station of the eukaryotic endomembrane system, an intricate network of organelles engaged in control of membrane trafficking and the processing of various cellular components. Previous ideas of compartmental stability within this network are gradually being reshaped by concepts describing a biochemical continuum of hybrid organelles whose constitution is regulated by compartmental maturation. Membrane lipid composition and lipid signaling processes make fundamental contributions to compartmentalization strategies that are themselves critical for organizing cellular architecture and biochemical activities.

Dissecting the role of histidine kinase and HOG1 mitogen-activated protein kinase signalling in stress tolerance and pathogenicity of Parastagonospora nodorum on wheat.

The HOG1 mitogen-activated protein kinase (MAPK) pathway is activated through two-component histidine kinase (HK) signalling. This pathway was first characterized in the budding yeast Saccharomyces cerevisiae as a regulator of osmotolerance. The fungus Parastagonospora nodorum is the causal agent of septoria nodorum blotch of wheat.

A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis.

Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles.

PITPs as targets for selectively interfering with phosphoinositide signaling in cells.

Sec14-like phosphatidylinositol transfer proteins (PITPs) integrate diverse territories of intracellular lipid metabolism with stimulated phosphatidylinositol-4-phosphate production and are discriminating portals for interrogating phosphoinositide signaling. Yet, neither Sec14-like PITPs nor PITPs in general have been exploited as targets for chemical inhibition for such purposes. Herein, we validate what is to our knowledge the first small-molecule inhibitors (SMIs) of the yeast PITP Sec14.

Golgi membrane dynamics and lipid metabolism.

The striking morphology of the Golgi complex has fascinated cell biologists since its discovery over 100 years ago. Yet, despite intense efforts to understand how membrane flow relates to Golgi form and function, this organelle continues to baffle cell biologists and biochemists alike. Fundamental questions regarding Golgi function, while hotly debated, remain unresolved.

Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphatase.

In the Golgi apparatus, lipid homeostasis pathways are coordinated with the biogenesis of cargo transport vesicles by phosphatidylinositol 4-kinases (PI4Ks) that produce phosphatidylinositol 4-phosphate (PtdIns4P), a signaling molecule that is recognized by downstream effector proteins. Quantitative analysis of the intra-Golgi distribution of a PtdIns4P reporter protein confirms that PtdIns4P is enriched on the trans-Golgi cisterna, but surprisingly, Vps74 (the orthologue of human GOLPH3), a PI4K effector required to maintain residence of a subset of Golgi proteins, is distributed with the opposite polarity, being most abundant on cis and medial cisternae. Vps74 binds directly to the catalytic domain of Sac1 (K(D) = 3.

The oxysterol-binding protein superfamily: new concepts and old proteins.

The Kes1 OSBP (oxysterol-binding protein) is a key regulator of membrane trafficking through the TGN (trans-Golgi network) and endosomal membranes. We demonstrated recently that Kes1 acts as a sterol-regulated rheostat for TGN/endosomal phosphatidylinositol 4-phosphate signalling. Kes1 utilizes its dual lipid-binding activities to integrate endosomal lipid metabolism with TORC1 (target of rapamycin complex 1)-dependent proliferative pathways and transcriptional control of nutrient signalling.

Sec14 like PITPs couple lipid metabolism with phosphoinositide synthesis to regulate Golgi functionality.

An interface coordinating lipid metabolism with proteins that regulate membrane trafficking is necessary to regulate Golgi morphology and dynamics. Such an interface facilitates the membrane deformations required for vesicularization, forms platforms for protein recruitment and assembly on appropriate sites on a membrane surface and provides lipid co-factors for optimal protein activity in the proper spatio-temporally regulated manner. Importantly, Sec14 and Sec14-like proteins are a unique superfamily of proteins that sense specific aspects of lipid metabolism, employing this information to potentiate phosphoinositide production.

A sterol-binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing.

Kes1, and other oxysterol-binding protein superfamily members, are involved in membrane and lipid trafficking through trans-Golgi network (TGN) and endosomal systems. We demonstrate that Kes1 represents a sterol-regulated antagonist of TGN/endosomal phosphatidylinositol-4-phosphate signaling. This regulation modulates TOR activation by amino acids and dampens gene expression driven by Gcn4, the primary transcriptional activator of the general amino acid control regulon.

Resurrection of a functional phosphatidylinositol transfer protein from a pseudo-Sec14 scaffold by directed evolution.

Sec14-superfamily proteins integrate the lipid metabolome with phosphoinositide synthesis and signaling via primed presentation of phosphatidylinositol (PtdIns) to PtdIns kinases. Sec14 action as a PtdIns-presentation scaffold requires heterotypic exchange of phosphatidylcholine (PtdCho) for PtdIns, or vice versa, in a poorly understood progression of regulated conformational transitions. We identify mutations that confer Sec14-like activities to a functionally inert pseudo-Sec14 (Sfh1), which seemingly conserves all of the structural requirements for Sec14 function.

Sss1p is required to complete protein translocon activation.

Protein translocation across the endoplasmic reticulum membrane occurs at the Sec61 translocon. This has two essential subunits, the channel-forming multispanning membrane protein Sec61p/Sec61α and the tail-anchored Sss1p/Sec61γ, which has been proposed to "clamp" the channel. We have analyzed the function of Sss1p using a series of domain mutants and found that both the cytosolic and transmembrane clamp domains of Sss1p are essential for protein translocation.

Zebrafish class 1 phosphatidylinositol transfer proteins: PITPbeta and double cone cell outer segment integrity in retina.

Phosphatidylinositol transfer proteins (PITPs) in yeast co-ordinate lipid metabolism with the activities of specific membrane trafficking pathways. The structurally unrelated metazoan PITPs (mPITPs), on the other hand, are an under-investigated class of proteins. It remains unclear what biological activities mPITPs discharge, and the mechanisms by which these proteins function are also not understood.