Nav: Home

New target identified to combat deadly allergic reactions

October 24, 2016

Researchers in France have identified a molecular motor that controls the release of inflammatory factors that cause severe and fatal allergic reactions. The study, "Kinesin-1 controls mast cell degranulation and anaphylaxis through PI3K-dependent recruitment to the granular Slp3/Rab27b complex," which will be published online October 24 ahead of issue in The Journal of Cell Biology, suggests that targeting this motor may be a new way to treat patients undergoing anaphylactic shock.

Mast cells are a type of white blood cell localized in most tissues of the body that fight off parasitic infections by releasing histamine and other inflammatory factors contained in secretory granules. But allergens can also trigger granule release, and, if this happens simultaneously in mast cells throughout the body, it can provoke a life-threatening anaphylactic response that leads to facial swelling, difficulty breathing, a drop in blood pressure, and fainting. Currently, the main treatment for anaphylaxis is to immediately inject patients with epinephrine using devices such as the EpiPen from the pharmaceutical company Mylan NV.

When mast cells are activated by allergens bound to immunoglobulin E antibodies, secretory granules move along microtubules to the periphery of the cells, where they can fuse with the plasma membrane and release their contents. Two teams of researchers led by Ulrich Blank (CNRS) of the Center of Research on Inflammation (CNRS) and Gaël Ménasché (INSERM) of the Imagine Institute in Paris, France, investigated the role of kinesin-1, a motor protein that transports various cargoes along microtubules.

The researchers created mice whose mast cells lacked a key subunit of kinesin-1 called Kif5b. These animals were much less sensitive to allergen-induced anaphylaxis. Their mast cells showed lower levels of secretory granule release because the granules were no longer transported to the plasma membrane upon mast cell activation.

The researchers discovered that, in response to mast cell stimulation, a signaling pathway involving the enzyme phosphatidylinositol 3-kinase triggers kinesin-1's association with a protein complex on the surface of secretory granules. One member of this complex, Rab27b, has previously been shown to regulate mast cell secretion. Blank and Ménasché's team found that depleting the other member, Slp3, also impaired secretory granule transport and release, similar to the effects of removing Kif5b.

"The fact that mice lacking Kif5b in their mast cells exhibited very low levels of passive, systemic anaphylaxis suggests that kinesin-1 could be a valuable new therapeutic target for controlling allergic reactions," Ménasché says.
-end-
Munoz, I., et al. 2016. J. Cell Biol.http://dx.doi.org/10.1083/jcb.201605073

About The Journal of Cell Biology

The Journal of Cell Biology (JCB) features peer-reviewed research on all aspects of cellular structure and function. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JCB provides free online access to many article types from the date of publication and to all archival content. Established in 1955, JCB is published by The Rockefeller University Press. For more information, visit jcb.org.

Follow us on Twitter at @JCellBiol and @RockUPress.

Rockefeller University Press

Related Cell Biology Articles:

Biochemists develop new way to control cell biology with light
Researchers at the University of Alberta have developed a new method of controlling biology at the cellular level using light.
Molecular biology: Fingerprinting cell identities
Every cell has its own individual molecular fingerprint, which is informative for its functions and regulatory states.
Cell biology: Take the mRNA train
Messenger RNAs bearing the genetic information for the synthesis of proteins are delivered to defined sites in the cell cytoplasm by molecular motors.
Designer switches of cell fate could streamline stem cell biology
Researchers at the University of Wisconsin-Madison have developed a novel strategy to reprogram cells from one type to another in a more efficient and less biased manner than previous methods.
Live cell imaging of asymmetric cell division in fertilized plant cells
Plant biologists have succeeded for the first time in visualizing how egg cells in plants divides unequally (asymmetric cell division) after being fertilized.
Vortex rings may aid cell delivery, cell-free protein production
Cornell researchers have devised a method for producing toroid-shaped particles through a process called vortex ring freezing.
Original cell type does not affect iPS cell differentiation to blood
The effectiveness of reprogramming cells into blood cells is thought to depend on the original cell type and reprogramming method.
Misleading images in cell biology
Virtually all membrane proteins have been reported to be organized as clusters on cell surfaces, when in fact many of them are just single proteins which have been counted multiple times.
Roadmap for advanced cell manufacturing shows path to cell-based therapeutics
An industry-driven consortium has developed a national roadmap designed to chart the path to large-scale manufacturing of cell-based therapeutics for use in a broad range of illnesses including cancer, neuro-degenerative diseases, blood and vision disorders and organ regeneration and repair.
Copernicus Award 2016 for German-Polish Collaboration in Molecular Cell Biology
Researchers from Göttingen and Warsaw receive award from the DFG and the Foundation for Polish Science (FNP) / Award ceremony to take place on June 7, 2016 in Warsaw.

Related Cell Biology Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".