New paper provides insights into the logic of neurotrophin signaling through the p75 neurotrophin receptor

Cell Reports publishes today our latest paper describing a structure-function map of the death domain of the p75 neurotrophin receptor (Charalampopoulos et al. 2012)

Structural determinants underlying signaling specificity in the tumor necrosis factor receptor superfamily (TNFRSF) are poorly characterized and it is unclear whether different signaling outputs can be genetically dissociated. The p75 neurotrophin receptor (p75NTR), also known as TNFRSF16, is a key regulator of trophic and injury responses in the nervous system. In this paper, we describe a genetic approach to dissect p75NTR signaling and decipher its underlying logic. Structural determinants important for regulation of cell death, NF-kB and RhoA pathways were identified in the p75NTR death domain. Pro-apoptotic and pro-survival pathways mapped onto non-overlapping epitopes, demonstrating that different signaling outputs can be genetically separated in p75NTR. Dissociation of JNK and caspase-3 activities indicated that JNK is necessary but not sufficient for p75NTR-mediated cell death. RIP2 recruitment and RhoGDI release were mechanistically linked, indicating that competition for DD binding underlies cross-talk between NF-kB and RhoA pathways in p75NTR signaling. These results provide new insights into the logic of p75NTR signaling and pave the way for a genetic dissection of p75NTR function and physiology.

Read the full paper HERE.

Research associate joins NUS group to assist with research on death receptor structure and function

Gao Jian Fang has a Bachelor’s degree in pharmaceutical engineering from Beijing University of Chinese Medicine and a Master’s degree in medicinal chemistry from Peking Union Medical College, Tsinghua University. Before joining our group, she worked as a Research Assistant at the Department of Anatomy of the  Yong Loo Lin School of Medicine, NUS, on a project aimed at identiying therapeutic strategies to inhibit microglia-mediated neuroinflammation and cognitive impairment after brain trauma.

New postdoc fellow joins NUS group to study in vivo physiology of p75NTR signaling

Kazuhiro Tanaka obtained a PhD in Pharmacy  in 2005 from the Graduate School of Pharmaceutical Sciences, Osaka University, Japan, under the direction of Prof. Akemichi Baba, for studies on PACAP signaling and its effects on behavior. He subsequently did postdoctoral studies on astrocyte biology and patophysiology under Dr. Yutaka Koyama at Osaka-Ohtani University and on stroke models under Prof. Ong Wei Yi at the Department of Pharmacology, National Uniersity of Singapore. His new studies will focus on elucidating the physiological functions of death receptor signaling in the developing and injured nervous system using mouse models carrying mutations in the p75ntr gene.

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