In class Assignment 2

APRIL 2021 ASBMB TODAY 23

JOURNAL NEWS

age-related disease. DOI:10.1074/mcp.RA120.002301

The duality of coagulation factor V

Factor V, or FV, is a glycoprotein that has a dual role as both an antico- agulation and procoagulation cofac- tor. Central to its opposing functions is the proteolytic removal of its central B-domain, and researchers seek to un- derstand the mechanisms surrounding this functional switch.

In a paper published in the Journal of Biological Chemistry, Teod- olinda Petrillo and colleagues at the Children’s Hospital of Pennsylvania describe their study of how bond cleavage in the B-domain influ- ences interactions between FV and FV-short, a physiologically relevant isoform with a shortened B-domain, and tissue factor pathway inhibitor alpha, or TFPIα. Using clotting assays, chromatography, fluorescent aniso- tropy and biochemical analyses, the authors demonstrated that key forms of FV, including FV-short, are physi- ologic ligands for TFPIα. The authors speculate that strategies that target the interaction of TFPIα with these different forms of FV may provide a new way to strengthen or dampen the coagulation system. DOI: 10.1074/jbc.RA120.016341

Finding sites that control lipid metabolism

Triglycerides are stored within lipid droplets, which are essential for energy metabolism. The triglycerides are broken down into fatty acids and glycerol via lipid droplet-associated proteins, such as perilipin, or PLIN. Researchers are interested in PLIN5 because it is expressed in various highly oxidative tissues and influences lipid metabolism in response to

A new way to absorb dietary iron Iron, a mineral found in every cell of the human body, combines with

proteins to form the hemoglobin required to transport oxygen. The body also needs iron for physical growth, neurological development and criti- cal biochemical functions, making it an essential nutrient. However, iron in excess is toxic, and the body has no physiological means to excrete that excess. Instead, levels are regulated by iron absorption.

Dietary iron mainly exists in two forms: heme and nonheme. Plant- based and fortified foods are a source of nonheme iron, whereas meat, seafood and poultry supply both heme and nonheme iron. The National Heart, Lung and Blood Institute estimates that 20% of women, 50% of pregnant women and 3% of men have an iron deficiency, which is the most common cause of anemia, a decrease in red blood cells. This deficiency can be treated with iron supplements. However, absorption of available supplements is inefficient, and it often takes several months to reestablish normal iron levels.

Researchers recently identified nicotianamine-iron chelate, or NA- Fe2+, as a new form of bioavailable iron present in mice, chickens and plant-based foods. However, researchers know little about the mecha- nisms responsible for NA-Fe2+ absorption from its dietary sources. In a recent article in the Journal of Biological Chemistry, Yoshiko Murata and a team of researchers in Japan identified the proton-coupled amino acid transporter, or PAT1, as the principal channel through which NA- Fe2+ is absorbed. Using cultured cells modified to no longer contain the PAT1 protein, electrophysiological analyses of PAT1 overexpression in aquatic frog oocytes and experiments with mice, the authors demonstrat- ed the uptake of NA-Fe2+ into the epithelium of the proximal jejunum and iron appearance in spleen, liver and kidney.

These findings confirm that NA-Fe2+ is a bioavailable source of iron, uncover the possible mechanism by which NA-Fe2+ is absorbed in the mammalian intestine, and may drive development of improved iron supplements. DOI: 10.1074/jbc.RA120.015861

— Anand Rao

24 ASBMB TODAY APRIL 2021

JOURNAL NEWS

Rajamani Selvam ([email protected]) is an Oak Ridge Institute for Science and Education research fellow at the U.S. Food and Drug Administration in Maryland. Follow her on Twitter @Rajaman06539874

Anand Rao ([email protected]) is an ASBMB science communi- cator. Follow him on Twitter @AnandRaoPhD.

phosphorylation — a post-trans- lational modification in which phosphate groups are added to the protein. Previous work has established that the phosphorylation of serine residues is enough to activate PLIN5- regulated lipid breakdown.

In a recent paper published in the Journal of Lipid Research, Stacey N. Keenan and colleagues at the University of Melbourne describe how they identified phosphorylation sites of serine residues in PLIN5 and determined which of these sites are functional using cultured cells and mice. Three phosphorylation sites in PLIN5 were identified: S155, S161 and S163. Out of these, S155 is a functionally important phosphoryla- tion site for lipid metabolism, while the others did not show any effect on lipid breakdown in cultured cells. Using PLIN5 S155A–mutant mice, the researchers showed a reduction in triglyceride breakdown, suggesting a critical role for PLIN5 as a regula- tor for lipid metabolism. This work provides new information on the role of PLIN5 in controlling lipid metabolism. DOI: 10.1194/jlr.RA120001126

Sorting out sinking phagocytosis

Phagocytosis, the receptor-medi- ated ingestion of cellular particles, is the major function of immune cells such as macrophages and neutrophils. Yet more than 100 years after Élie Metschnikoff — the scientist credited with discovering phagocytes — de- veloped his theory of phagocytosis, scientists still know little about the processes that govern this cellular ingestion process. Researchers have described two structurally distinct modes of phagocytosis: phagocytic cup formation, whereby the mem- brane extends outward and engulfs

Nicole Lynn (nalynn@ g.ucla.edu) is a graduate student at the University of California, Los Angeles in the chemistry and biochemistry department.

the particle, and sinking phagocytosis, the inward engulfment of particles. A number of receptors that activate downstream signaling pathways initi- ate phagocytosis. One such receptor, CR3, is thought to drive sinking phagocytosis. However, evidence of this receptor’s involvement is sparse.

In a recent study published in the Journal of Biological Chemistry, Stefan Walbaum and colleagues at the University of Münster in Germany isolated resident macrophages from normal unaltered mice and mice genetically altered to lack CR3 recep- tors to investigate how macrophages engage and internalize particles. Using RNA-sequence analysis, genetic experiments and real-time 3D imag- ing, the researchers showed that CR3 receptors indeed regulate a mode of sinking phagocytosis and also are involved in the formation and closing of Fc receptors for immunoglobulin G, or fragment crystallizable gamma receptor–controlled phagocytic cups that extend outward to engulf particles. DOI: 10.1016/j.jbc.2021.100256

24 ASBMB TODAY APRIL 2021

ASBMB CAREER CENTER

Make your next move.

Browse jobs in academia and industry and get a free résumé review.

careers.asbmb.org