UCSF Journal Club: Recent Research by UCSF Scientists
Alexandra Greer
Science Editor
IMMUNOLOGY: Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Liang, H.E. et al. (Locksley). Nature Immunology. 13(1):58-66.
Cytokines are specific molecules, of which there are hundreds, that promote specific immune functions in different types of cells. For example, the cytokine IL-2 promotes the growth and survival of newly-activated T-cells. Because of this specificity, certain illnesses can be characterized by the release of specific cytokines; allergy is typified by the cytokines IL-4 and IL-13. However, precisely which types of immune cells secrete IL-4 and -13 has been up for debate. In this paper, researchers have meticulously identified which immune cells secrete IL-4 and IL-13 in allergic immunity and pinpoint GATA-3 as the transcription factor controlling IL-13 production in particular. While T-follicular helper cells and basophils produce IL-4 only, innate helper-like 2 cells produce IL-13 only, and T-helper 2 cells produce both.
CELL BIOLOGY: The adaptor protein CRK is a pro-apoptotic transducer of endoplasmic reticulum stress. Austgen, K.; Johnson, E.T.; Park, T.J.; Curran, T.; Oakes, S.A. Nature Cell Biology. 14(1):87-92.
The endoplasmic reticulum (ER) is a cellular organelle that, with ribosomes, takes care of protein generation and folding in the cell. When the ER gets overwhelmed with misfolded or unfolded proteins, the ER sends stress signals that can result in cell death. In fact, this process contributes to the cellular degeneration seen in diseases such as type II diabetes and some neurodegenerative disorders. Here, researchers wanted to elucidate the molecular mechanisms that cause the ER to initiate apoptosis due to folding stress. To do this, they biochemically isolated multiple fractions from cells undergoing ER stress and added them to mitochondria to see which fractions induced apoptosis. Once they identified the fraction, mass spectrometry identified the main active protein as CRK, an adaptor protein with previously unknown function. Without CRK, or with certain protein domains of CRK mutated, cells are strongly resistant to ER-stress-induced apoptosis.
CELL BIOLOGY: Distribution and Expression of Non-Neuronal Transient Receptor Potential (TRPV) Ion Channels in Rosacea. Sulk, M. et al. (Steinhoff). Journal of Investigative Dermatology. December 22. [Epub ahead of print]
Rosacea is a common, yet poorly understood skin condition that causes variable symptoms, usually involving flushing and/or rashes on the face. The cause of rosacea is not known and is thought to potentially involve the nervous system, because of the increased skin sensitivity, vasodilation, and skin flushing seen in many individuals. Cells outside of the classical definition of the nervous system - such as immune cells or skin cells - can express some neurotransmitter receptors, making them potential players in the condition as well. Here, researchers investigated the expression of transient receptor potential ion channels (TRPV channels) on various cells in the skin of rosacea patients as compared to healthy controls. Different types of rosacea were found to have elevated levels of TRPV channels in multiple cell types, indicating them as a possible target for novel therapeutics.
MICROBIOLOGY: Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection. Jäger, S. et al. (Krogan). Nature. December 21. [Epub ahead of print]
APOBEC3G is a cellular antiviral that prevents viral replication in our cells by deaminating viral DNA, resulting in hypermutation that causes the viral genome to become jumbled and useless. In response, the HIV virus uses the protein Vif to inactivate APOBEC3G, thus allowing for uninterrupted viral replication in the cell. Vif, therefore, is an attractive target for HIV therapeutics, as interfering with its function would allow our own cells to fight the virus. Here, researchers found that Vif requires direct binding to the transcription factor CBF-β in order to inactivate APOBEC3G by promoting its ubiquitination and degradation. These findings have direct implications for the development of new antiretrovirals that target Vif/CBF-β interactions.
Alexandra Greer is a fourth-year biomedical sciences student.
This article appeared in the January 12, 2012 issue of Synapse.