A cysteine-rich form of Xenopus neuregulin induces the expression of acetylcholine receptors in cultured myotubes.
Neuregulin-1 (NRG-1) has diverse functions in neural development, and one of them is to up regulate the expression of acetylcholine receptors (AChRs) at muscle fibers during the formation of neuromuscular junctions. NRG-1 has two prominent alternative splicing sites at the N-terminus; it could be an immunoglobulin (Ig)-like domain named Ig-NRG-1 or an apolar cysteine-rich domain (CRD) named CRD-NRG-1. cDNAs encoding Xenopus CRD-NRG-1 were isolated by cross-hybridization with Xenopus Ig-NRG-1 cDNA fragment. The amino acid sequence of Xenopus CRD-NRG-1 is 45 to 70% identical to the human, rat, and chick homologs. Similar to Ig-NRG-1, two variation sites within CRD-NRG-1 were identified at the spacer domain with 0 or 43 amino acids inserted and at the C-terminus of the EGF-like domain to derive either alpha or beta isoform. Two transcripts encoding CRD-NRG-1, approximately 7.5 and approximately 9.0 kb, were revealed in adult brain and spinal cord, but the expression in muscle was below the detectable level. The recombinant Xenopus CRD-NRG-1 when applied onto cultured myotubes was able to induce the tyrosine phosphorylation of ErbB receptors and the expression of AChR. The AChR-inducing activity of CRD-NRG-1 was precipitated by anti-NRG-1 antibody but not by heparin. In situ hybridization showed a strong expression of CRD-NRG-1 mRNA in developing brain, spinal cord, and myotomal muscles of Xenopus embryo. Similar to the results in other species, both CRD-NRG-1 and Ig-NRG-1 may play a role in the developing Xenopus neuromuscular junctions.
Yang
J F
JF
Department of Biology and Biotechnology Research Institute, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China.
Zhou
H
H
Choi
R C
RC
Ip
N Y
NY
Peng
H B
HB
Tsim
K W
KW
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003001:Cloning, Molecular; D003545:Cysteine / Q000235:genetics; D004625:Embryo, Nonmammalian; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D020880:Neuregulins; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011950:Receptors, Cholinergic / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
D006023:Glycoproteins; D009414:Nerve Growth Factors; D020880:Neuregulins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D003545:Cysteine