Neuroglycan C, a novel member of the neuregulin family

Kinugasa, Yumi; Ishiguro, Hiroshi; Tokita, Yoshihito; Oohira, Atsuhiko; Ohmoto, Hiroshi; Higashiyama, Shigeki

doi:10.1016/j.bbrc.2004.07.066

Cited by 56 publications

(50 citation statements)

References 25 publications

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“…It is known that the EGF domain of NGC activates ErbB3 as a direct ligand (38). Furthermore, a deficiency of NGC causes functional abnormalities of synapses in the early postnatal period (37).…”

Section: Discussionmentioning

confidence: 99%

Neuroglycan C Is a Novel Midkine Receptor Involved in Process Elongation of Oligodendroglial Precursor-like Cells

Ichihara-Tanaka

Oohira

Rumsby

et al. 2006

Journal of Biological Chemistry

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Midkine is a heparin-binding growth factor that promotes cell attachment and process extension in undifferentiated bipolar CG-4 cells, an oligodendroglial precursor cell line. We found that CG-4 cells expressed a non-proteoglycan form of neuroglycan C, known as a part-time transmembrane proteoglycan. We demonstrated that neuroglycan C before or after chondroitinase ABC treatment bound to a midkine affinity column. Neuroglycan C lacking chondroitin sulfate chains was eluted with 0.5 M NaCl as a major fraction from the column. We confirmed that CG-4 cells expressed two isoforms of neuroglycan C, I, and III, by isolating cDNA. Among three functional domains of the extracellular part of neuroglycan C, the chondroitin sulfate attachment domain and acidic amino acid cluster box domain showed affinity for midkine, but the epidermal growth factor domain did not. Furthermore, cell surface neuroglycan C could be cross-linked with soluble midkine. Process extension on midkine-coated dishes was inhibited by either a monoclonal antineuroglycan C antibody C1 or a glutathione S-transferase-neuroglycan C fusion protein. Finally, stable transfectants of B104 neuroblastoma cells overexpressing neuroglycan C-I or neuroglycan C-III attached to the midkine substrate, spread well, and gave rise to cytoskeletal changes. Based on these results, we conclude that neuroglycan C is a novel component of midkine receptors involved in process elongation. Midkine (MK),2 a heparin-binding growth factor, is strongly expressed at the mid-embryonic stage of development and is preferentially expressed in the kidney after birth (1, 2). MK is a 13-kDa protein with about 50% sequence identity to pleiotrophin (PTN), which is also called heparin-binding growth-associated molecule (3, 4). MK promotes neurite outgrowth and migration in neuronal cells isolated from the embryonic brain (5-7) and prevents apoptosis (8, 9). MK also promotes the migration of inflammatory leukocytes (10) and thereby plays a key role in the etiology of neointima formation (10), renal injury (11, 12), rheumatoid arthritis (13), and intraperitoneal adhesion after surgery (14). So far, protein-tyrosine phosphatase (7, 15), anaplastic lymphoma kinase (16), low density-lipoprotein receptor-related protein-1 (17), low density lipoprotein receptor-related protein 6 (9), and integrin ␣4␤1 and ␣6␤1 (18) have been identified as MK receptors. These molecules cooperate during MK signaling, possibly as a receptor complex (18). However, not all the molecules serving as MK receptors have been clarified. Importantly, we do not know whether a function specific to a class of cells such as neurite extension requires another receptor to transmit the specific signal or not. Here, we report that a cell surface molecule is specifically expressed in the nervous system as a component of the MK receptor in cells extending processes.When undifferentiated CG-4 cells, an oligodendrocyte precursor cell line, are cultured on dishes coated with MK or PTN, they quickly extend processes and adopt bipolar shapes ...

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Section: Discussionmentioning

confidence: 99%

Neuroglycan C Is a Novel Midkine Receptor Involved in Process Elongation of Oligodendroglial Precursor-like Cells

Ichihara-Tanaka

Oohira

Rumsby

et al. 2006

Journal of Biological Chemistry

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“…EGF [7,8], transforming growth factor-α (TGF-α) [9,10], and amphiregulin [11] uniquely bind EGFR. ErbB3 binds neuregulin-1 [12][13][14][15][16] and neuregulin-2 [17][18][19][20] and uniquely binds Neuroglycan C [21]. ErbB4 is also able to bind neuregulin-1 and neuregulin-2 and uniquely binds neuregulin-3 [22], neuregulin-4 [23], and tomoregulin [24] as well.…”

Section: Receptor Overviewmentioning

confidence: 99%

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Wieduwilt

Moasser

2008

Cell. Mol. Life Sci.

628

503

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The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy.

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“…In light of the fact that OPCs have recently been shown to receive functional synapses from neurons (Lin and Bergles, 2004), the finding of high levels of secreted peptides within OPCs intriguingly suggests that these cells may release these peptides on receiving synaptic input. Another interesting finding is the detection of neuroglycan C gene expression, which has been recently characterized as a novel ErbB3/ErbB2 ligand (Kinugasa et al, 2004). This is interesting, because ErbB2 activation enhances OL differentiation and survival (Fernandez et al, 2000;Park et al, 2001;Kim et al, 2003), suggesting the possibility that, in the early stages of OL differentiation, OPC-derived neuroglycan C could provide support for newly forming OLs until they tightly wrap axons, whereupon the axonally expressed ErbB2 ligand neuregulin could then support myelinating OLs (Barres and Raff, 1999).…”

Section: Analysis Of the Genes Most Highly Expressed By Opcsmentioning

confidence: 99%

Functional Genomic Analysis of Oligodendrocyte Differentiation

Dugas¹,

Tai²,

Speed³

et al. 2006

J. Neurosci.

294

353

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To better understand the molecular mechanisms governing oligodendrocyte (OL) differentiation, we have used gene profiling to quantitatively analyze gene expression in synchronously differentiating OLs generated from pure oligodendrocyte precursor cells in vitro. By comparing gene expression in these OLs to OLs generated in vivo, we discovered that the program of OL differentiation can progress normally in the absence of heterologous cell-cell interactions. In addition, we found that OL differentiation was unexpectedly prolonged and occurred in at least two sequential stages, each characterized by changes in distinct complements of transcription factors and myelin proteins. By disrupting the normal dynamic expression patterns of transcription factors regulated during OL differentiation, we demonstrated that these sequential stages of gene expression can be independently controlled. We also uncovered several genes previously uncharacterized in OLs that encode transmembrane, secreted, and cytoskeletal proteins that are as highly upregulated as myelin genes during OL differentiation. Last, by comparing genomic loci associated with inherited increased risk of multiple sclerosis (MS) to genes regulated during OL differentiation, we identified several new positional candidate genes that may contribute to MS susceptibility. These findings reveal a previously unexpected complexity to OL differentiation and suggest that an intrinsic program governs successive phases of OL differentiation as these cells extend and align their processes, ensheathe, and ultimately myelinate axons.

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Neuroglycan C, a novel member of the neuregulin family

Cited by 56 publications

References 25 publications

Neuroglycan C Is a Novel Midkine Receptor Involved in Process Elongation of Oligodendroglial Precursor-like Cells

Neuroglycan C Is a Novel Midkine Receptor Involved in Process Elongation of Oligodendroglial Precursor-like Cells

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Functional Genomic Analysis of Oligodendrocyte Differentiation

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