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Mol Neurobiol (2009) 40:122138 DOI 10.1007/s12035-009-8076-x
Olfactomedin Domain-Containing Proteins: Possible Mechanisms of Action and Functionsin Normal Development and Pathology
Stanislav I. Tomarev & Naoki Nakaya
Received: 2 April 2009 /Accepted: 14 June 2009 /Published online: 26 June 2009 # Humana Press Inc. 2009
Abstract A family of olfactomedin domain-containing proteins consists of at least 13 members in mammals. Although the first protein belonging to this family, olfactomedin, was isolated and partially characterized from frog olfactory neuroepithelim almost 20 years ago, the functions of many family members remain elusive. Most of the olfactomedin domain-containing proteins, similar to frog olfactomedin, are secreted glycoproteins that demonstrate specific expression patterns. Other family members are membrane-bound proteins that may serve as receptors. More than half of the olfactomedin domain-containing genes are expressed in neural tissues. Data obtained over the last several years demonstrate that olfactomedin domain-containing proteins play important roles in neuro-genesis, neural crest formation, dorsal ventral patterning, cellcell adhesion, cell cycle regulation, and tumorigenesis and may serve as modulators of critical signaling pathways (Wnt, bone morphogenic protein). Mutations in two genes encoding myocilin and olfactomedin 2 were implicated in glaucoma, and a growing number of evidence indicate that other genes belonging to the family of olfactomedin domain-containing proteins may contribute to different human disorders including psychiatric disorders. In this review, we summarize recent advances in understanding the possible roles of these proteins with special emphasis on the proteins that are preferentially expressed and function in neural tissues.
Keywords Olfactomedin . Myocilin . Glaucoma . Eye . Brain . Neurogenesis . Olfactomedin domain-containing protein . Neural crest
Introduction
Olfactomedin was first described in 1991 as a novel 57-kDa glycoprotein that was exclusively expressed in the frog olfactory neuroepithelim [1]. Olfactomedin undergoes posttranslational modifications and is able to form homodimers and high molecular weight aggregates via intermolecular disulfides. High levels of olfactomedin expression and deposition at the chemosensory surface of the olfactory epithelium suggested that this protein plays a role in chemoreception [1]. Cloning of complementary DNA (cDNA) encoding olfactomedin and analysis of its expression pattern confirmed that olfactomedin was expressed only in olfactory neuroepithelium of frogs and that its amino acid sequence showed no homology to any known protein [2]. Subsequent experiments by many laboratories over the following 15 years...