Soluble Receptors

Secreted Reelin Receptor

Science's STKE  19 Nov 2002:
Vol. 2002, Issue 159, pp. tw428-TW428
DOI: 10.1126/stke.2002.159.tw428

The secreted protein Reelin regulates movement and cell-cell interactions during embryonic brain development. It accomplishes this by activating signaling cascades in target neurons that express an appropriate Reelin receptor such as ApoE receptor 2 (ApoER2), a member of the LDL receptor family. The ApoER2 transcript undergoes differential splicing to generate numerous receptor variants, one of which is predicted to encode a furin cleavage site that would generate a secreted extracellular ligand-binding domain. Koch et al. show that this cleaved form of ApoER2 is indeed generated by furin in transfected cells. Treatment of primary mouse neuronal cultures with purified, soluble ApoER2 fragment inhibited the Reelin signaling pathway. The specific transcript was also detected in primary neurons and only in the mouse cerebrum. This isoform of ApoER2 could act as a dominant-negative receptor by blocking the interaction of Reelin with cognate receptors on the surface of neurons.

S. Koch, V. Strasser, C. Hauser, D. Fasching, C. Brandes, T. M. Bajari, W. J. Schneider, J. Nimpf, A secreted soluble form of ApoE receptor 2 acts as a dominant negative receptor and inhibits Reelin signaling. EMBO J. 21, 5996-6004 (2002). [Abstract] [Full Text]