Human Molecular Genetics, Vol 5, 1109-1115, Copyright © 1996 by Oxford University Press
EI Rugarli, C Ghezzi, V Valsecchi and A 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.
ARTICLES
The Kallmann syndrome gene product expressed in COS cells is cleaved on the cell surface to yield a diffusible component
Telethon Institute of Genetics and Medicine, Milano, Italy.
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