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Adult function of GFRα1 in medial habenula neurons


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.

Genetic Dissection of Neurotrophin Signaling through the p75 Neu
Genetic dissection of neurotrophin signaling through the p75 neurotrophin  receptor
Charalampopoulos, I, Vicario, A, Pediaditakis, I ,Gravanis, A, Simi, A and Ibanez, CF  (2012)
Cell Reports, 10.1016/j.celrep.2012.11.009
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Carlos Ibanez appointed as Wallenberg Scholar

The Knut and Alice Wallenberg Foundation has today appointed Carlos Ibanez as a Wallenberg Scholar. The award includes a research grant of 15 million Swedish crowns over 5 years. Quote from the Foundation’s website: “The Foundation’s purpose is to support Swedish research and thereby strengthen Sweden as a research nation. Since 2009, we have appointed a total of 46 Wallenberg Scholars. The appointed researchers all belong to the international research forefornt in all areas of science, with an emphasis on medicine and the natural sciences, says Peter Wallenberg Jr., vice chairman of the Knut and Alice Wallenberg Foundation.” Read the text of the announcement (in Swedish) HERE and press release from Karolinska Institute HERE.

Carolyn Marks

“Regulatory mechanisms in olfactory system assembly and function”
7 December 2012

Abstract from KI website

External examiner:
Prof. Charles Greer
Yale University,
New Haven, CT

This thesis is based on the following papers:

I. Nguyen MQ, Zhou Z, Marks CA, Ryba NJ, Belluscio L. Prominent roles for odorant receptor coding sequences in allelic exclusion. Cell 2007 Nov 30;131(5):1009-17 [Abstract]

II. Nguyen MQ, Marks CA, Belluscio L, Ryba NJ. Early expression of odorant receptors distorts the olfactory circuitry. J Neurosci. 2010 Jul 7;30(27):9271-9 [Abstract]

III. Marks CA, Cheng K, Cummings DM, Belluscio L. Activity-dependent plasticity in the olfactory intrabulbar map. J Neurosci. 2006 Nov 1;26(44):11257-66 [Abstract]

IV. Marks, CA, Belluscio L, Ibanez CF. Critical role of GFRa1 in the development and function of the mouse olfactory system. J. Neurosci. 2012, Nov 28;32 (48): 17306-17320 [PDF]

V. Marks CA, Belluscio L, Ibanez CF. A cell-autonomous role of GFRa1 in the development of olfactory bulb GABAergic interneurons. Manuscript