Abstract:
:The protein anosmin-1, coded by the KAL1 gene responsible for the X-linked form of Kallmann syndrome (KS), exerts its biological effects mainly through the interaction with and signal modulation of fibroblast growth factor receptor 1 (FGFR1). We have previously shown the interaction of the third fibronectin-like type 3 (FnIII) domain and the N-terminal region of anosmin-1 with FGFR1. Here, we demonstrate that missense mutations reported in patients with KS, C172R and N267K did not alter or substantially reduce, respectively, the binding to FGFR1. These substitutions annulled the chemoattraction of the full-length protein over subventricular zone (SVZ) neuronal precursors (NPs), but they did not annul it in the N-terminal-truncated protein (A1Nt). We also show that although not essential for binding to FGFR1, the cysteine-rich (CR) region is necessary for anosmin-1 function and that FnIII.3 cannot substitute for FnIII.1 function. Truncated proteins recapitulating nonsense mutations found in KS patients did not show the chemotropic effect on SVZ NPs, suggesting that the presence behind FnIII.1 of any part of anosmin-1 produces an unstable protein incapable of action. We also identify the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway as necessary for the chemotropic effect exerted by FGF2 and anosmin-1 on rat SVZ NPs.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Esteban PF,Murcia-Belmonte V,García-González D,de Castro Fdoi
10.1111/jnc.12104subject
Has Abstractpub_date
2013-03-01 00:00:00pages
708-20issue
5eissn
0022-3042issn
1471-4159journal_volume
124pub_type
杂志文章abstract::Retinal ganglion cells transmit the visual signal from the retina to the brain. We have previously shown that the activator protein 2 (AP-2)δ (TFAP2D) transcription factor is expressed in one third of ganglion cells in developing retina suggesting a specialized role for these AP-2δ-expressing cells. Here, we address t...
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1111/jnc.12783
更新日期:2014-09-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章,多中心研究
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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更新日期:1982-05-01 00:00:00
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pub_type: 杂志文章
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abstract::The ontogenesis of alpha 2-adrenoceptors and GTP-binding proteins and their coupling activity were investigated in telencephalon membranes of developing rats. The manganese-induced elevation of [3H]clonidine binding was increased in an age-dependent manner but the guanosine 5'-O-(3-thio)triphosphate-induced decrease i...
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