Expanding drug development horizons: Receptor behaviors observed in living cell membranes

Feb 07, 2011

Unprecedented single molecule imaging movies of living cell membranes, taken by a research team based at Kyoto University and the University of New Mexico, have clarified a decades-old enigma surrounding receptor molecule behaviors. The results, appearing in the latest issue of the Journal of Cell Biology, promise to open the door to new possibilities for drug development.

The work focuses on G protein-coupled receptors (GPCRs), a class of in cell membranes that comprise the largest superfamily in the human genome. In spite of being the focus of roughly half of modern drug development due to their key role in signaling across the membrane, until now it has not been well understood how GPCRs relay signals from the outside world into cells' interiors.

For over 15 years, debate regarding GPCRs' signaling mechanisms has centered on whether these molecules work alone (as monomers) or in pairs (). Using formyl-peptide receptors (FPRs) as a model GPCR, the research team found that the two views are both partially correct.

"By developing a super-quantitation single-molecule imaging method, in which GPCR molecules are inspected one by one in living cell membranes," explained Rinshi Kasai of Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) and lead author of the paper, "we are now able to actually 'see' that each individual FPR molecule moves around in the cell membrane, endlessly interconverting between monomers and dimers with different partners, completing each cycle within a quarter of a second."

According to iCeMS Professor Akihiro Kusumi, "We obtained a parameter called the dissociation constant, which will allow us to predict numbers of and dimers if the total number of GPCRs in a cell is known. The ability of scientists to obtain such key numbers will be essential for understanding GPCR signaling, as well as defects leading to diseases from the neuronal to the immune systems. The implications for drug design, blocking signal amplification by monomer-dimer interconversion, are profoundly important."

The research team, funded in part by the Japan Science and Technology Agency (JST) and the Japanese education ministry MEXT, anticipates that their findings will have a broad impact on the further study of signal transduction in the and conceptual and methodological development for drug discovery.

Explore further: How plant cell compartments change with cell growth

More information: The article, "Full characterization of GPCR monomer–dimer dynamic equilibrium by single molecule imaging" by Rinshi S. Kasai, Kenichi G. N. Suzuki, Eric R. Prossnitz, Ikuko Koyama-Honda, Chieko Nakada, Takahiro K. Fujiwara, and Akihiro Kusumi, was published online in the February 7, 2011 issue of the Journal of Cell Biology.

add to favorites email to friend print save as pdf

Related Stories

Study Unravels Detail of 'Most Important' Cellular Signal

Dec 03, 2009

(PhysOrg.com) -- A new study provides crucial details that promise to help researchers better understand, and perhaps fine-tune with drugs, one of the most important signaling mechanisms in human cells, according to a study ...

Recommended for you

How plant cell compartments change with cell growth

16 hours ago

A research team led by Kiminori Toyooka from the RIKEN Center for Sustainable Resource Science has developed a sophisticated microscopy technique that for the first time captures the detailed movement of ...

Plants can 'switch off' virus DNA

17 hours ago

A team of virologists and plant geneticists at Wageningen UR has demonstrated that when tomato plants contain Ty-1 resistance to the important Tomato yellow leaf curl virus (TYLCV), parts of the virus DNA ...

A better understanding of cell to cell communication

17 hours ago

Researchers of the ISREC Institute at the School of Life Sciences, EPFL, have deciphered the mechanism whereby some microRNAs are retained in the cell while others are secreted and delivered to neighboring ...

A glimpse at the rings that make cell division possible

18 hours ago

Forming like a blown smoke ring does, a "contractile ring" similar to a tiny muscle pinches yeast cells in two. The division of cells makes life possible, but the actual mechanics of this fundamental process ...

User comments : 0