A Lipid Transfer Protein Signaling Axis Exerts Dual Control of Cell-Cycle and Membrane Trafficking Systems

Huang, Jin; Mousley, Carl J.; Dacquay, Louis; Maitra, Nairita; Drin, Guillaume; He, Chi; Ridgway, Neale D.; Tripathi, Ashutosh; Kennedy, Michael A.; Kennedy, Brian K.; Liu, Wenshe Ray; Baetz, Kristin; Polymenis, Michael; Bankaitis, Vytas A.

doi:10.1016/j.devcel.2017.12.026

Cited by 33 publications

(43 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, members of the StARkin-related and Sec14 domain-containing (CRAL-TRIO) superfamilies of LTPs have been classically defined as PtdIns-transfer proteins (PITPs) that are thought to function by redistributing PtdIns from donor to acceptor membranes, likely as part of a heterotypic exchange involving additional lipid species such as phosphatidylcholine or phosphatidic acid (Cockcroft and Carvou, 2007; Grabon et al, 2019). Despite their name, it is yet to be understood how these PITPs function within intact cells; although unique PITPs are increasingly linked to specific signaling modalities in studies of model organisms (Xie et al, 2018; Huang et al, 2018). In addition to the autonomous PITPs, recent work has also suggested that PtdIns can be used as a lipid cargo by the relatively promiscuous TUbular LIPid-binding (TULIP) family of LTPs that possess synaptotagmin-like mitochondrial lipid-binding protein (SMP) domains; including a report of preferential PtdIns transfer from the ER to the PM by the SMP domain-containing protein TMEM24 following PLC activation and PtdIns(4,5)P 2 hydrolysis (Lees et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Defining the Subcellular Distribution and Metabolic Channeling of Phosphatidylinositol

Pemberton

Kim

Sengupta

et al. 2019

Preprint

View full text Add to dashboard Cite

1 Pemberton et al. characterize a molecular toolbox for the visualization and manipulation of 2 phosphatidylinositol (PtdIns) within intact cells. Results using these approaches define the steady-state 3 distribution of PtdIns across subcellular membrane compartments as well as provide new insights into the 4 relationship between PtdIns availability and polyphosphoinositide turnover. 5 6 7 Abstract 8Phosphatidylinositol (PtdIns) is an essential structural component of eukaryotic membranes that also 9 serves as the common precursor for polyphosphoinositide (PPIn) lipids. Despite the recognized importance 10 of PPIn species for signal transduction and membrane homeostasis, there is still a limited understanding of 11 how the dynamic regulation of PtdIns synthesis and transport contributes to the turnover of PPIn pools. To 12 address these shortcomings, we capitalized on the substrate selectivity of a bacterial enzyme, PtdIns-specific 13 PLC, to establish a molecular toolbox for investigations of PtdIns distribution and availability within intact cells. 14 In addition to its presence within the ER, our results reveal low steady-state levels of PtdIns within the plasma 15 membrane (PM) and endosomes as well as a relative enrichment of PtdIns within the cytosolic leaflets of the 16 Golgi complex, peroxisomes, and outer mitochondrial membranes. Kinetic studies also demonstrate the 17 requirement for sustained PtdIns supply from the ER for the maintenance of monophosphorylated PPIn 18 species within the PM, Golgi complex, and endosomal compartments. 19

show abstract

Section: Discussionmentioning

confidence: 99%

Defining the Subcellular Distribution and Metabolic Channeling of Phosphatidylinositol

Pemberton

Kim

Sengupta

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…A remarkable development that has come from the Sec14 studies is that lipid transfer proteins function as an antagonistic pair in coupling PtdIns4P signaling with TGN/endosomal membrane trafficking. That is, the action of the pro-trafficking Sec14 is countered by the action of the Kes1/Osh4, a PtdIns4P/ergosterol exchange protein that functions as a trafficking brake in this system (23,146,149,(153)(154)(155)(156). Moreover, the antagonistic actions of Kes1 and Sec14 in TGN/endosomal membrane trafficking extend to cell cycle contexts associated with cellular commitment to a new round of cell division.…”

Section: The Antagonistic Relationship Of Sec14 With Lipid Exchange Pmentioning

confidence: 99%

The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes

Grabon

Bankaitis

McDermott

2019

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

P 3 ]. Yeasts (Saccharomyces) synthesize all of these except PtdIns(3,4)P 2 and PtdIns(3,4,5)P 3. This cohort of molecules is produced by a series of reversible phosphorylation and dephosphorylation reactions catalyzed by phosphoinositide kinases (PIKs) and phosphatases, respectively, that target the inositol headgroup at positions C3, C4, and C5 (1, 2). These chemically distinct lipids, although small in number, control an impressively large set of intracellular activities. How is such diversification of biological function achieved? Current views for how PtdIns and phosphoinositide signaling are diversified focus on regulatory mechanisms that include: the regulation and localization of the enzymes that produce, degrade, or sequester phosphoinositides; the identities of the effector proteins that recognize these Abstract Phosphoinositides are key regulators of a large number of diverse cellular processes that include membrane trafficking, plasma membrane receptor signaling, cell proliferation, and transcription. How a small number of chemically distinct phosphoinositide signals are functionally amplified to exert specific control over such a diverse set of biological outcomes remains incompletely understood. To this end, a novel mechanism is now taking shape, and it involves phosphatidylinositol (PtdIns) transfer proteins (PITPs). The concept that PITPs exert instructive regulation of PtdIns 4-OH kinase activities and thereby channel phosphoinositide production to specific biological outcomes, identifies PITPs as central factors in the diversification of phosphoinositide signaling. There are two evolutionarily distinct families of PITPs: the Sec14-like and the StAR-related lipid transfer domain (START)-like families. Of these two families, the START-like PITPs are the least understood. Herein, we review recent insights into the biochemical, cellular, and physiological function of both PITP families with greater emphasis on the START-like PITPs, and we discuss the underlying mechanisms through which these proteins regulate phosphoinositide signaling and how these actions translate to human health and disease.-Grabon, A., V. A. Bankaitis, and M. I. McDermott. The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes.

show abstract

“…Despite these studies, it is still not clear how PITPs function within intact cells, including whether they efficiently transport PtdIns or alternatively regulate PLC activity. In contrast, functional studies using more complex in vivo models have associated diverse PITPs with specific roles in membrane trafficking and signal transduction in defined cellular contexts . It has also been postulated that PITPs may contribute to the allosteric control of other membrane‐associated proteins or serve as modules for presenting bound PtdIns to modifying enzymes, with the most compelling evidence coming from yeast studies using Sec14 .…”

Section: Phosphatidylinositol Synthesis and Transportmentioning

confidence: 99%

Integrated regulation of the phosphatidylinositol cycle and phosphoinositide‐driven lipid transport at ER‐PM contact sites

Pemberton

Kim

Balla

2019

Traffic

View full text Add to dashboard Cite

Among the structural phospholipids that form the bulk of eukaryotic cell membranes, phosphatidylinositol (PtdIns) is unique in that it also serves as the common precursor for low-abundance regulatory lipids, collectively referred to as polyphosphoinositides (PPIn). The metabolic turnover of PPIn species has received immense attention because of the essential functions of these lipids as universal regulators of membrane biology and their dysregulation in numerous human pathologies. The diverse functions of PPIn lipids occur, in part, by orchestrating the spatial organization and conformational dynamics of peripheral or integral membrane proteins within defined subcellular compartments. The emerging role of stable contact sites between adjacent membranes as specialized platforms for the coordinate control of ion exchange, cytoskeletal dynamics, and lipid transport has also revealed important new roles for PPIn species. In this review, we highlight the importance of membrane contact sites formed between the endoplasmic reticulum (ER) and plasma membrane (PM) for the integrated regulation of PPIn metabolism within the PM. Special emphasis will be placed on non-vesicular lipid transport during control of the PtdIns biosynthetic cycle as well as toward balancing the turnover of the signaling PPIn species that define PM identity. K E Y W O R D SCRAL-TRIO, intracellular transport, lipid transfer protein, membrane contact sites, nonvesicular lipid transport, oxysterol-binding protein-related protein, phosphatidylinositol, phosphatidylinositol transfer protein, phosphoinositides, phospholipid metabolism, signal transduction, StARkin, TUbular LIPid-binding

show abstract

A Lipid Transfer Protein Signaling Axis Exerts Dual Control of Cell-Cycle and Membrane Trafficking Systems

Cited by 33 publications

References 63 publications

Defining the Subcellular Distribution and Metabolic Channeling of Phosphatidylinositol

Defining the Subcellular Distribution and Metabolic Channeling of Phosphatidylinositol

The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes

Integrated regulation of the phosphatidylinositol cycle and phosphoinositide‐driven lipid transport at ER‐PM contact sites

Contact Info

Product

Resources

About