August 2010

Meeting Theme: Lipid and Membrane Metabolism

Sphingolipids

Sphingolipids facilitate the formation of membrane microdomains and act as signaling molecules that regulate a myriad of cellular processes. The “Sphingolipid Metabolism and Biological Regulation” session will feature newly described sphingolipid regulatory mechanisms.

Lipid and Membrane Metabolism


Session: Current Topics in Phosphoinositide Biology and Signaling
Ptdlns-4-kinase Regulation of Protein Sorting in the Golgi Apparatus, Christopher S. Burd, University of Pennsylvania School of Medicine

Phosphatidylinositol-4-phosphate Signaling in Drosophila, Julie Brill, The Hospital for Sick Children

Coordination of Lipid Metabolism with Phosphoinositide Signaling by Phosphatidylinositol Transfer Proteins of the Sec14 Superfamily, Vytas A. Bankaitis, University of North Carolina School of Medicine

Session: Sphingolipid Metabolism and Biological Regulation
Sphingosine Phosphate Lyase and the DNA Damage Response, Julie D. Saba, Children’s Hospital Oakland
Research Institute

The Asthma-associated ORM/ORMDL Family Proteins Mediate Sphingolipid Homeostasis, Jonathan S. Weissman, Howard Hughes Medical Institute Investigator, University of California, San Francisco

Biology and Enzymology of Sphingolipid Synthesis, Teresa M. Dunn, Uniformed Services University of the Health Sciences

Session: Phospholipase D and Phosphatidic Acid Signaling
Chemical Biology Approaches to Defining Phosphatidic Acid Signaling Pathways, H. Alex Brown, Vanderbilt University School of Medicine

The Role of Phospholipase D in Vesicle Fusion, Aaron Neiman, Stony Brook University

Lipid Signaling Regulated by pH: Phosphatidic Acid as a pH Biosensor, Christopher J. R. Loewen, University of British Columbia

Session: Biology of Neutral Lipid Metabolism and Trafficking
The Ins and Outs of Fat Metabolism: New Insights from Yeast, Sepp D. Kohlwein, University of Graz

Intracellular Cholesterol Transport, Frederick R. Maxfield, Weill Cornell Medical College

Intra-organelle Sterol Transfer Activity of Oxysterol Binding Proteins, Neale Ridgway, Dalhousie University

Julie D. Saba (Children’s Hospital Oakland Research Institute) will discuss her recent work on the role of sphingosine-1-phosphate lyase in DNA repair as an example of the underinvestigated problem of lipid signaling in the nucleus. The committed enzyme of sphingolipid synthesis, SPT, is also expected to be highly regulated, but the mechanisms are elusive. Jonathan S. Weissman (University of California, San Francisco) will present new insights into sphingolipid homeostasis, the role of the ORM/ORMDL family of proteins as regulators of that process and how this regulatory circuit provides new paradigms for etiologies of asthma. Finally, Teresa M. Dunn (Uniformed Services University of the Health Sciences) will describe novel stimulatory subunits of SPT that modulate acyl-CoA substrate selectivity and may hold the key to a molecular basis for the HSAN1 inherited peripheral neuropathy.

Phospholipases D

Phospholipases D (PLD) hydrolyze phosphatidylcholine (PtdCho) to phosphatidic acid (PtdOH) and choline. The potent signaling functions attributed to PtdOH, when coupled with the regulation of PLD activity by phosphoinositides, small GTPases and protein kinases, identifies these enzymes as potentially central integrators of phospholipid metabolism and signaling. Yet, the biological activities of these enzymes have been frustratingly difficult to discern— particularly in mammalian cells.

Research into this problem will be on display in the “Phospholipase D and Phosphatidic Acid Signaling” session. H. Alex Brown (Vanderbilt University School of Medicine) will describe the characterization of recently developed small molecule inhibitors of mammalian PLDs, the cellular effects associated with acute PLD inactivation and new mass spectrometry-based techniques for molecular tracking of PtdOH.

The presentations by Aaron Neiman (Stony Brook University) and Christopher J. R. Loewen (University of British Columbia) will focus on signaling roles for PtdOH. Neiman will discuss the regulation of PLD1 and the roles of PtdOH in developmentally regulated re-orientation of membrane trafficking and vesicle fusion during sporulation in yeast. Loewen will describe evidence that PtdOH plays a previously unappreciated role as a membrane pH sensor.

Neutral Lipids

The recent linkage of excessive storage of triacylglycerols (TAGs) to obesity and type 2 diabetes has spurred studies that elevate lipid droplets (LDs), major TAG storage depots, to the status of an intracellular organelle.

In the “Biology of Neutral Lipid Metabolism and Trafficking” session, Sepp D. Kohlwein (University of Graz) will discuss recent evidence of an unexpected link between fatty acid and triacylglycerol metabolism and the transcriptional regulation of phospholipid synthesis.

Aberrant cholesterol transport and storage underlie many diseases, and these processes have been studied intensively for many years. Nonetheless, fundamental aspects of intracellular sterol transport and distribution remain poorly understood. Frederick R. Maxfield (Weill Cornell Medical College) will present current progress on intracellular sterol trafficking and distribution. And finally, Neale Ridgway (Dalhousie University) will discuss how the enigmatic oxysterol binding proteins coordinate sterol trafficking and metabolism.

Teresa M. Dunn (tdunn@usuhs.mil) is a professor and chair of the department of biochemistry and molecular biology at the Uniformed Services University of the Health Sciences. Vytas A. Bankaitis (vytas@med.unc.edu) is a professor and chair of cell and developmental biology at the University of North Carolina School of Medicine.

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