Anosmin-1 underlying the X chromosome-linked Kallmann syndrome is an adhesion molecule that can modulate neurite growth in a cell-type specific manner.
Anosmin-1 is an extracellular matrix glycoprotein which underlies the X chromosome-linked form of Kallmann syndrome. This disease is characterized by hypogonadism due to GnRH deficiency, and a defective sense of smell related to the underdevelopment of the olfactory bulbs. This study reports that anosmin-1 is an adhesion molecule for a variety of neuronal and non-neuronal cell types in vitro. We show that cell adhesion to anosmin-1 is dependent on the presence of heparan sulfate and chondroitin sulfate glycosaminoglycans at the cell surface. A major cell adhesion site of anosmin-1 was identified in a 32 amino acid (32R1) sequence located within the first fibronectin-like type III repeat of the protein. The role of anosmin-1 as a substrate for neurite growth was tested on either coated culture dishes or monolayers of anosmin-1-producing CHO cells. In both experimental systems, anosmin-1 was shown to be a permissive substrate for the neurite growth of different types of neurons. Mouse P5 cerebellar neurons cultured on anosmin-1 coated wells developed long neurites; the 32R1 peptide was found to underly part of this neurite growth activity. When the cerebellar neurons were cultured on anosmin-1-producing CHO cells, neurite growth was reduced as compared to wild-type CHO cells; in contrast, no difference was observed for E18 hippocampal and P1 dorsal root ganglion neurons in the same experimental system. These results indicate that anosmin-1 can modulate neurite growth in a cell-type specific manner. Finally, anosmin-1 induced neurite fasciculation of P5 cerebellar neuron aggregates cultured on anosmin-1-producing CHO cells. The pathogenesis of the olfactory defect in the X-linked Kallmann syndrome is discussed in the light of the present results and the recent data reporting the immunohistochemical localisation of anosmin-1 during early embryonic development.
Soussi-Yanicostas
N
N
Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, 75724 Paris Cedex 15, France.
Faivre-Sarrailh
C
C
Hardelin
J P
JP
Levilliers
J
J
Rougon
G
G
Petit
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology; D006224:Cricetinae; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology; D008040:Genetic Linkage; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D006801:Humans; D017436:Kallmann Syndrome / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009830:Olfactory Bulb / Q000002:abnormalities; D014162:Transfection; D014960:X Chromosome / Q000235:genetics
C076266:ANOS1 protein, human; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules