Research Highlights

Short, accessible synopses of recent important articles concerning signalling pathways.

March 2008

• B-cell signalling: Synapse formation wRAPped up with help from RAC2

  

  When a B cell encounters membrane-bound antigen, signalling through the B-cell receptor (BCR) induces cytoskeletal reorganization and morphological changes that lead to the formation of an immunological synapse. Two papers published in Immunity describe a crucial role for the RAP and RAC2 GTPases in this process.

  Original research paper Nature Reviews Immunology 8 168 doi:10.1038/nri2291

• Signal transduction: New tricks for old JNKs

  

  Although c-Jun N-terminal kinases (JNKs) are among the most abundant protein kinases in the brain, their physiological functions in neurons are yet to be established. Huganir and colleagues now identify two glutamate-receptor subunits as JNK substrates and show how JNKs regulate their trafficking.

  Original research paper Nature Reviews Neuroscience 9 164 - 165 doi:10.1038/nrn2342

• Stem cells: Harvest in the right season

  

  Understanding the release of haematopoietic stem cells (HSCs) from the bone marrow into the bloodstream is the basis for bone marrow transplantation procedures. However, the molecular mechanisms that regulate this process are not well understood. A study in Nature now shows that the mobilization of HSCs follows a physiologically regulated circadian rhythm.

  Original research paper Nature Reviews Molecular Cell Biology 9 185 doi:10.1038/nrm2355

• Allergy and Asthma: What 'drives' IL-4 versus IL-13 signalling?

  

  Interleukin-4 (IL-4) and IL-13 are crucially involved in the development of allergic responses through their induction of T helper 2 (T_H2) cells and promotion of IgE production. Both of these cytokines use the common -chain (_c)-related IL-4 receptor -chain (IL-4R) to signal through three cytokine–receptor combinations: IL-4 signals through the type I receptor IL-4R–_c, and both IL-4 and IL-13 can signal through the type II receptor IL-4R–IL-13R1. This study describes the crystal structures of these three ligand–receptor combinations, which provide insights into the mechanisms and consequences of receptor degeneracy versus specificity.

  Original research paper Nature Reviews Immunology 8 166 - 167 doi:10.1038/nri2283

• Metabolism: The importance of polarity

  

  LKB1 is a serine/threonine kinase that is associated with the regulation of energy homeostasis and cell polarity. Somatic loss-of-function mutations in STK11 (which encodes LKB1) account for Peutz–Jeghers syndrome (PJS), which is associated with an increased risk of developing gastrointestinal neoplasms and pancreatic cancer. Nabeel Bardeesy, Ronald DePinho and colleagues provide evidence for a link between cell polarity and, when deregulated, the development of pancreatic cancer.

  Original research paper Nature Reviews Cancer 8 162 - 163 doi:10.1038/nrc2337