Alternative titles; symbols
HGNC Approved Gene Symbol: BOC
Cytogenetic location: 3q13.2 Genomic coordinates (GRCh38): 3:113,210,926-113,287,459 (from NCBI)
CDON (608707) and BOC are cell surface receptors of the immunoglobulin (Ig)/fibronectin type III (FNIII; see 135600) repeat family involved in myogenic differentiation. CDON and BOC are coexpressed during development, form complexes with each other in a cis fashion, and are related to each other in their ectodomains, but each has a unique long cytoplasmic tail.
By low stringency screening of a human fetal brain cDNA library using rat Cdon as probe, followed by EST database analysis and further screening, Kang et al. (2002) obtained a cDNA encoding BOC. The 1,113-amino acid BOC protein contains 4 Ig repeats, followed by 3 FNIII repeats, a single-pass transmembrane domain, and a 238-residue intracellular region. The domain structure of BOC is similar to that of CDON, and the 2 proteins share 38 to 80% amino acid identity in the individual extracellular domains. The intracellular region of BOC, however, is unrelated to that of CDON. In situ hybridization analysis revealed that, like Cdon, Boc was strongly expressed in dorsal neural tube, somites, and dermomyotomes during murine embryonic development. Northern blot analysis detected a 5-kb transcript in myoblasts in the absence of Ras (190020) transformation. BOC was expressed in most adult human tissues tested, with highest levels in skeletal muscle and small intestine.
By biochemical and morphologic analyses, Kang et al. (2002) showed that overexpression of BOC or CDON resulted in precocious differentiation of myoblasts. Immunoprecipitation analysis showed that CDON and BOC formed complexes in a cis fashion via association between both their respective extracellular and intracellular domains, probably through direct interactions. In contrast with CDON, the intracellular region of BOC was not essential for its ability to positively regulate differentiation. Kang et al. (2002) concluded that BOC is dependent on CDON for activity and that CDON-BOC complexes function to regulate myogenic differentiation.
Wegorzewska et al. (2003) showed that stable overexpression of CDO or BOC in a human rhabdomyosarcoma cell line led to enhanced expression of 2 markers of muscle cell differentiation, troponin T (TNNT1; 191041) and myosin heavy chain (see 160730), and to increased formation of elongated, myosin heavy chain-positive myotubes. Wegorzewska et al. (2003) proposed that CDO and BOC play a role in the inverse relationship between differentiation and transformation of cells in the skeletal muscle lineage.
Kang et al. (2003) showed by coimmunoprecipitation, immunoblot, and confocal microscopic analyses that CDO and BOC formed complexes with promyogenic cadherins, such as N-cadherin (116806), at sites of cell-cell contact. Ectodomain CDO and BOC fusion proteins interacted with the ectodomain of N-cadherin. Immunoprecipitation analysis also showed interaction of the respective intracellular regions, indicating that the associations of the proteins occurred in cis. Biochemical and microscopic analyses demonstrated that cells expressing CDO lacking the first FNIII repeat were unable to associate with N-cadherin and interfered with myogenic differentiation in vitro.
In the spinal cord, Sonic hedgehog (SHH; 600725) is secreted by the floor plate to control the generation of distinct classes of ventral neurons along the dorsoventral axis. Genetic and in vitro studies have shown that SHH also later acts as a midline-derived chemoattractant for commissural axons. Okada et al. (2006) showed that 2 Robo (see 602430)-related proteins, BOC and CDON (608707), bind specifically to SHH and are therefore candidate receptors for the action of SHH as an axon guidance ligand. BOC is expressed by commissural neurons, and targeted disruption of BOC in mouse resulted in the misguidance of commissural axons toward the floor plate. RNA interference-mediated knockdown of Boc impaired the ability of rat commissural axons to turn towards an ectopic source of Shh in vitro. Taken together, Okada et al. (2006) concluded that BOC is essential as a receptor for SHH in commissural axon guidance.
Sanders et al. (2013) found that, in mesenchymal cells of the developing chick limb bud, SHH is produced in the form of a particle that remains associated with the cell via long cytoplasmic extensions that span several cell diameters. They also found that in SHH-responding cells, specific subsets of SHH coreceptors, including CDON and BOC, actively localize and substantially colocalize in specific microdomains within filopodial extensions, far from the cell body. Stabilized interactions are formed between filopodia containing SHH ligand and those containing coreceptors over a long range. Sanders et al. (2013) concluded that contact-mediated release propagated by specialized filopodia contributes to the delivery of SHH at a distance.
The International Radiation Hybrid Mapping Consortium mapped the BOC gene to chromosome 3 (RH93384).
Kang, J.-S., Feinleib, J. L., Knox, S., Ketteringham, M. A., Krauss, R. S. Promyogenic members of the Ig and cadherin families associate to positively regulate differentiation. Proc. Nat. Acad. Sci. 100: 3989-3994, 2003. [PubMed: 12634428] [Full Text: https://doi.org/10.1073/pnas.0736565100]
Kang, J.-S., Mulieri, P. J., Hu, Y., Taliana, L., Krauss, R. S. BOC, an Ig superfamily member, associates with CDO to positively regulate myogenic differentiation. EMBO J. 21: 114-124, 2002. [PubMed: 11782431] [Full Text: https://doi.org/10.1093/emboj/21.1.114]
Okada, A., Charron, F., Morin, S., Shin, D. S., Wong, K., Fabre, P. J., Tessier-Lavigne, M., McConnell, S. K. Boc is a receptor for Sonic hedgehog in the guidance of commissural axons. Nature 444: 369-373, 2006. [PubMed: 17086203] [Full Text: https://doi.org/10.1038/nature05246]
Sanders, T. A., Llagostera, E., Barna, M. Specialized filopodia direct long-range transport of SHH during vertebrate tissue patterning. Nature 497: 628-632, 2013. [PubMed: 23624372] [Full Text: https://doi.org/10.1038/nature12157]
Wegorzewska, M., Krauss, R. S., Kang, J.-S. Overexpression of the immunoglobulin superfamily members CDO and BOC enhances differentiation of the human rhabdomyosarcoma cell line RD. Molec. Carcinogen. 37: 1-4, 2003. [PubMed: 12720294] [Full Text: https://doi.org/10.1002/mc.10121]