Aarhus Universitet

Christian Bjerggaard Vægter

Sortilin Associates with Trk Receptors to Enhance Anterograde Transport and Signaling by Neurotrophins

Publikation: KonferencebidragPosterForskning

  • Institut for Medicinsk Biokemi

Neurotrophins (NT) are neuronal growth factors essential for development and maintenance of the nervous system. They are released in two forms with opposing biological functions. The proforms induce apoptosis by engaging a death signaling complex comprising the p75NTR neurotrophin receptor and Sortilin (Nykjaer et al, Nature 427:843-48, 2004). By contrast, their mature counterparts stimulate neuronal survival and differentiation by binding to p75NTR in association with one of the tyrosine receptor kinases TrkA, -B, and -C, respectively. The dual role of p75NTR as a regulator of both death and survival has been extensively studied in knockout mouse models. We recently generated a Sortilin knockout mouse model (Sort1-/-) and showed that the receptor is essential for p75NTR to induce death of neurons during certain stages of development and aging and upon brain injury (Jansen et al, Nat. Neurosci. 10:1449-57, 2007). In order to examine if Sortilin, like p75NTR, might also facilitate survival signaling by mature NTs we generated mice deficient for both p75NTR and Sortilin (Ngfr-/- x Sort1-/-). We demonstrate that the TrkA, -B and -C phenotypes present in the p75NTR null mouse (Ngfr-/-) are aggravated in the Sortilin/p75NTR double knockout mouse. Our findings suggest a novel and surprising function of Sortilin as a positive regulator of neuronal survival.

StatusUdgivet - 2010
BegivenhedFENS - Federation of European Neurosciences - Amsterdam, Holland
Varighed: 3 jul. 20107 jul. 2010


KonferenceFENS - Federation of European Neurosciences

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