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Story ideas from Molecular and Cellular Proteomics

Special April issue on mass spectrometry in the life sciences

American Society for Biochemistry and Molecular Biology

This month, Molecular & Cellular Proteomics will highlight some of the research presented at the 8th International Symposium on Mass Spectrometry in the Health and Life Sciences, held this past August in San Francisco. This Symposium described how recent advances in mass spectrometry have expanded our current knowledge about the vast protein networks inside cells and how they are regulated.

Mass spectrometry, an analytical technique that measures molecules on the basis of mass-to-charge ratio, has been gaining popularity in the biological arena. And with the power to analyze large samples on the order of several thousand molecules and the ability to distinguish various chemical signatures like phosphorylation, this technology has found a perfect home in the field of proteomics.

Notes MCP co-editor Ralph Bradshaw, Professor of Pharmaceutical Chemistry and Deputy Director of the Mass Spectrometry Facility at the University of California, San Francisco: "I believe the articles selected for this issue really capture the "flavor" of how mass spectrometry can aid and advance proteomics. These are great studies and some of them are right at the cutting edge of research."

The 10 articles comprising this special section include:

A Comprehensive Protein Map of a Stem Cell

Researchers have successfully identified over 5,000 proteins that are present in embryonic stem cells, tripling the size of previous results and in the process creating the largest quantified protein map to date.

Stem cells hold great potential in biology and medicine, but a host of questions lingers about how they operate and convert into other cells. To help answer these questions, researchers have begun taking a 'big picture' approach, identifying all the proteins that are expressed in stem cells.

Currently, around 1700 proteins have been identified in stem cells. Now, using mass spectrometry and special "heavy" amino acids (made with carbon-13), Matthias Mann and colleagues quantified 5111 distinct mouse stem cell proteins. As expected, a good portion of these proteins are involved in rapid cell growth, but overall the proteome encompassed a broad range of cell functions.

While this study may help uncover new clues to stem cell biology, it does raise the bar on the complexity of these important cells, considering they express at least 25% of all known mouse proteins.

"SILAC-labeling and proteome quantitation of mouse embryonic stem cells to a depth of 5111 proteins" by Johannes Graumann, Nina Hubner, Jeong Beom Kim, Kinarm Ko, Markus Moser, Chanchal Kumar, Jürgen Cox, Hans Schöler and Matthias Mann

Corresponding author: Matthias Mann, Department of Proteomics and Signal Transduction, Max-Planck-Institute for Biochemistry, Martinsried, Germany Phone: +49 (89) 8578 2557; Email:

A Novel Approach to Protein Variation in Synapses

Most brain functions, such as memory, require a sophisticated network of molecular interactions. However, experimental methods can only analyze a limited number of these interactions at a time.

Now, researchers have pioneered a novel approach, which enables them to analyze hundreds of network molecules simultaneously. Ralf Schoepfer, Al Burlingame and colleagues were able to compare the relative amount and, importantly, the phosphorylation status of proteins in the synapses of four different brain regions.

Synapses are the traffic intersections in our brain, the junctions between neurons where one cell passes information to its neighbor.

To better understand this flow of traffic, the scientists used mass spectrometry tools to analyze the post-synaptic density (PSD, the synapses' receiving end) of four brain regions in mice: cortex, midbrain, cerebellum, and hippocampus. In total, they examined over 2000 proteins and found some telling data about neuronal transmissions and memory.

For example, they observed that of all the brain regions, the hippocampus contained the highest levels of kinases and phosphatases, proteins that add and remove phosphate tags from other proteins. Phosphorylation provides a flexible and easily reversible way to regulate proteins, and this revelation suggests this may be how the hippocampus carries out one of its' main duties: collecting and consolidating memories.

This novel analysis should greatly aid efforts to understand how different parts of the brain handle their different jobs, and will also provides opportunities to investigate neuronal repair mechanisms and diseases such as Autism or Schizophrenia.

"Quantitative Analysis of Synaptic Phosphorylation and Protein Expression" by JC Trinidad, A Thalhammer, CG Specht, AJ Lynn, PR Baker, R Schoepfer, and AL Burlingame

Corresponding authors: Ralf Schoepfer, Laboratory for Molecular Pharmacology, University College London; Phone: +44-20-76797242, email:

Al Burlingame, Department of Pharmaceutical Chemistry, University of California, San Francisco; Phone: 415-476-5641, email:

Also in this special section:

"Proteomic studies of brassinosteroid signal transduction using prefractionation and 2-D DIGE" by Wenqiang Tang, Zhiping Deng, Juan A Oses-Prieto, Nagi Suzuki, Shengwei Zhu, Xin Zhang, Alma Burlingame, and Zhi-Yong Wang

Corresponding Author: Zhi-Yong Wang, Department of Plant Biology, Carnegie Institution of Washington, Stanford, CA; Email:

"Quantitative Proteomic Analysis of the Effects of Ionizing Radiation in Wild type and p53-K317R Knock-In Mouse Thymocytes" by Lisa M. Miller Jenkins, Sharlyn J. Mazur, Matteo Rossi, Olga Gaidarenko, Yang Xu and Ettore Appella

Corresponding Author: Ettore Appella, Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD; Phone: 301-402-4177, E-mail:

"Modulation of the phagosome proteome by interferon-gamma," by Isabelle Jutras, Mathieu Houde, Nathan Currier, Jonathan Boulais, Sophie Duclos, Sylvie LaBoissière, Eric Bonneil, Paul Kearney, Pierre Thibault, Eustache Paramithiotis, Patrice Hugo and Michel Desjardins

Corresponding Author: Michel Desjardins, Département de pathologie et biologie cellulaire, Université de Montréal, Québec; Phone: 514 343-7250, E-mail

"SIMAC - A phosphoproteomic strategy for the rapid separation of mono-phosphorylated from multiply phosphorylated peptides" by Tine Thingholm, Ole N. Jensen, Phillip J. Robinson and Martin Larsen

Corresponding author: Martin R. Larsen, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense; Phone: +45 6550 2475, E-mail:

"Statistical Similarities between Transcriptomics and Quantitative Shotgun Proteomics Data" by Norman Pavelka, Marjorie L. Fournier, Selene K. Swanson, Mattia Pelizzola, Paola Ricciardi-Castagnoli, Laurence Florens and Michael P. Washburn

Corresponding Author: Michael P. Washburn, Stowers Institute for Medical Research, Kansas City, MO; Phone: (816) 926-4457, E-mail:

"Combined enzymatic and data mining approaches for comprehensive phospho-proteome analyses; application to cell signaling events of interferon-gamma stimulated macrophages" by Maria Marcantonio, Matthias Trost, Mathieu Courcelles, Michel Desjardins and Pierre Thibault

Corresponding Author: Pierre Thibault, Institute for Research in Immunology and Cancer, Université de Montréal, Québec; Phone: +1 (514) 343-6910, E-mail:

"Coupled Global and Targeted Proteomics of Human Embryonic Stem Cells during Induced Differentiation" by Anastasia K. Yocum, Theresa E. Gratsch, Nancy Leff, John R. Strahler, Christie L. Hunter, Angela K. Walker, George Michailidis, Gilbert Omenn, K. Sue O'Shea and Philip C. Andrews

Corresponding Author: Anastasia K. Yocum, Department of Biological Chemistry, University of Michigan, Ann Arbor, MI; Phone: 215-284-3065, E-mail:

"CrossSearch, a User-friendly Search Engine for Detecting Chemically Cross-linked Peptides in Conjugated Proteins" by Owen W. Nadeau, Gerald J. Wyckoff, Justin E. Paschall, Antonio Artigues, Jessica Sage, Maria T. Villar and Gerald M. Carlson

Corresponding Author: Gerald M. Carlson, Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS; Phone: 913-588-7005, E-mail:


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