caa a22 4500 397574177 CHVBK 20180308164850.0 cr unu---uuuuu 161202e199608 xx s 000 0 eng 10.1093/hmg/5.8.1109 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.8.1109 The Kallmann Syndrome Gene Product Expressed in COS Cells is Cleaved on the Cell Surface to Yield a Diffusible Component [Elektronische Daten] [Elena I. Rugarli, Cristina Ghezzi, Valentina Valsecchi, Andrea Ballabio] Kallmann syndrome is characterized by hypogonadotropic hypogonadism and anosmia and caused by a defect of migration and targeting of gonadotropin-releasing hormone-secreting neurons and olfactory axons during embryonic development. We previously cloned the gene responsible for the X-linked form of the disease encoding a 680 amino acid protein, KAL, which displays the unusual combination of a protease inhibitor domain with fibronectin type III repeats. Previous expression studies by northern blot and RNA in situ hybridization in human and chick indicated that the gene is expressed at very low levels in the olfactory bulb during development. Therefore, low abundance of the protein has hampered a detailed biochemical characterization. By overexpressing both the human and chick KAL cDNAs in eukaryotic cells, we now provide evidence that KAL is a glycosylated peripheral membrane protein with an apparent molecular weight of approximately 100 kDa. We show that this 100 kDa protein is proteolytically processed on the cell membrane to yield a 45 kDa diffusible component, which is detectable with an antisera against the C-terminal part of the protein and binds tightly to cell surfaces. These data provide a first step toward understanding KAL function in neuronal interactions and neurite extension in the olfactory bulb and suggest that KAL might be a diffusible chemoattractant molecule for olfactory axons. © 1996 Oxford University Press Rugarli Elena I. Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, via Olgettina 58, 20132 Milano, Italy aut Ghezzi Cristina Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, via Olgettina 58, 20132 Milano, Italy aut Valsecchi Valentina Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, via Olgettina 58, 20132 Milano, Italy aut Ballabio Andrea Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, via Olgettina 58, 20132 Milano, Italy aut Human Molecular Genetics Oxford University Press 5/8(1996-08), 1109-1115 0964-6906 5:8<1109 1996 5 hmg https://doi.org/10.1093/hmg/5.8.1109 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.8.1109 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rugarli Elena I. Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, via Olgettina 58, 20132 Milano, Italy aut NATIONALLICENCE 700 1- Ghezzi Cristina Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, via Olgettina 58, 20132 Milano, Italy aut NATIONALLICENCE 700 1- Valsecchi Valentina Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, via Olgettina 58, 20132 Milano, Italy aut NATIONALLICENCE 700 1- Ballabio Andrea Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, via Olgettina 58, 20132 Milano, Italy aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/8(1996-08), 1109-1115 0964-6906 5:8<1109 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford