Neuregulins are a family of four structurally related proteins that are part of the EGF family of proteins. These proteins have been shown to have diverse functions in the development of the nervous system and play multiple essential roles in vertebrate embryogenesis including: cardiac development, Schwann cell and oligodendrocyte differentiation, some aspects of neuronal development, as well as the formation of neuromuscularsynapses.[2][3]
Neuregulin family
Structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4.[1]
Included in the family are heregulin; neu differentiation factor; acetylcholine receptor synthesis stimulator; glial growth factor; and sensory and motor-neuron derived factor.[4] Multiple family members are generated by alternate splicing or by use of several cell type-specific transcription initiation sites. In general, they bind to and activate the erbB family of receptor tyrosine kinases (erbB2 (HER2), erbB3 (HER3), and erbB4 (HER4)), functioning both as heterodimers and homodimers.
In mammals, neuregulin family members are the products of 4 genes NRG1, NRG2, NRG3 and NRG4 respectively.
The transmembrane forms of neuregulin 1 (NRG1) are present within synaptic vesicles, including those containing glutamate.[6] After exocytosis, NRG1 is in the presynaptic membrane, where the ectodomain of NRG1 may be cleaved off. The ectodomain then migrates across the synaptic cleft and binds to and activates a member of the EGF-receptor family on the postsynaptic membrane. This has been shown to increase the expression of certain glutamate-receptor subunits. NRG1 appears to signal for glutamate-receptor subunit expression, localization, and /or phosphorylation facilitating subsequent glutamate transmission.
The NRG1 gene has been identified as a potential gene determining susceptibility to schizophrenia by a combination of genetic linkage and association approaches.[6]
NRG1edit
NRG1 plays a role in synapse development, influencing the upregulation of acetylcholine receptor genes beneath the endplate after mammalian motor neurons have made synaptic contact with muscle fibres, hence its alternative name ARIA = Acetylcholine Receptor Inducing Activity.
Animal modelsedit
A study done on mice in early 2009 has indicated that when neuregulin-1\ErbB signalling is disrupted, the dendritic spines of neurons grow but do not fully form. This produced no immediate noticeable changes to brain development, but in adults there was a reduction of dendritic spines on neurons.[7][8] Glutamatergic signalling was markedly disrupted in the mice as a result of the experiment.
In fish, birds, and earthwormsedit
NRG-1,2,3 have been found in fish and birds.
mRNA similar to mammalian Pro-NRG2 precursor has been found in humus earthwormLumbricidae.
Referencesedit
^Nagata K, Kohda D, Hatanaka H, et al. (August 1994). "Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4". EMBO J. 13 (15): 3517–23. doi:10.1002/j.1460-2075.1994.tb06658.x. PMC395255. PMID 8062828.
^Vartanian T, Fischbach G, Miller R (1999). "Failure of spinal cord oligodendrocyte development in mice lacking neuregulin". Proc. Natl. Acad. Sci. U.S.A. 96 (2): 731–5. Bibcode:1999PNAS...96..731V. doi:10.1073/pnas.96.2.731. PMC15205. PMID 9892702.
^Yarden Y, Burden S (1997). "Neuregulins and their receptors: a versatile signaling module in organogenesis and oncogenesis". Neuron. 18 (6): 847–55. doi:10.1016/S0896-6273(00)80324-4. PMID 9208852.
^Schroering A, Carey DJ (1998). "Sensory and motor neuron-derived factor is a transmembrane heregulin that is expressed on the plasma membrane with the active domain exposed to the extracellular environment". J. Biol. Chem. 273 (46): 30643–50. doi:10.1074/jbc.273.46.30643. PMID 9804837.
^ abLemke G, Zhou M, Ghosh S, Harvey RP, Gulcher JR, Stefansson K, Gurney ME, Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Brynjolfsson J, Gunnarsdottir S, Ivarsson O, Chou TT, Hjaltason O, Birgisdottir B, Jonsson H, Gudnadottir VG, Gudmundsdottir E, Bjornsson A, Ingvarsson B, Ingason A, Sigfusson S, Hardardottir H, Lai D, Brunner D, Mutel V, Gonzalo A, Sainz J, Johannesson G, Andresson T, Gudbjartsson D, Manolescu A, Frigge ML, Kong A, Petursson H (2002). "Neuregulin 1 and susceptibility to schizophrenia". Am. J. Hum. Genet. 71 (4): 877–892. doi:10.1086/342734. PMC378543. PMID 12145742.
^"How Microscopic Changes To Brain Cause Schizophrenic Behavior In Mice".
^Barros CS, Calabrese B, Chamero P, Roberts AJ, Korzus E, Lloyd K, Stowers L, Mayford M, Halpain S, Müller U (February 2009). "Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system". Proc. Natl. Acad. Sci. U.S.A.106 (11): 4507–4512. Bibcode:2009PNAS..106.4507B. doi:10.1073/pnas.0900355106. PMC2657442. PMID 19240213.
neuregulin, family, four, structurally, related, proteins, that, part, family, proteins, these, proteins, have, been, shown, have, diverse, functions, development, nervous, system, play, multiple, essential, roles, vertebrate, embryogenesis, including, cardiac. Neuregulins are a family of four structurally related proteins that are part of the EGF family of proteins These proteins have been shown to have diverse functions in the development of the nervous system and play multiple essential roles in vertebrate embryogenesis including cardiac development Schwann cell and oligodendrocyte differentiation some aspects of neuronal development as well as the formation of neuromuscular synapses 2 3 Neuregulin familyStructure of the epidermal growth factor like domain of heregulin alpha a ligand for p180erbB 4 1 IdentifiersSymbolNeuregulinPfamPF02158InterProIPR002154SCOP21hrf SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryPDB1hae 1haf 1hre 1hrf Included in the family are heregulin neu differentiation factor acetylcholine receptor synthesis stimulator glial growth factor and sensory and motor neuron derived factor 4 Multiple family members are generated by alternate splicing or by use of several cell type specific transcription initiation sites In general they bind to and activate the erbB family of receptor tyrosine kinases erbB2 HER2 erbB3 HER3 and erbB4 HER4 functioning both as heterodimers and homodimers Contents 1 Neuregulin family members 2 NRG1 3 Animal models 4 In fish birds and earthworms 5 References 6 External linksNeuregulin family members editThe neuregulin family includes Neuregulin 1 NRG1 with numerous discovered isoforms stemming from alternative splicing Type I NRG1 alternative names Heregulin NEU differentiation factor NDF or acetylcholine receptor inducing activity ARIA Type II NRG1 alternative name Glial Growth Factor 2 GGF2 Type III NRG1 alternative name Sensory and motor neuron derived factor SMDF Type IV NRG1 Type V NRG1 Type VI NRG1 Types IV VI are proteins with 3 novel N terminal domains identified in 2004 5 Neuregulin 2 NRG2 Neuregulin 3 NRG3 Neuregulin 4 NRG4 In mammals neuregulin family members are the products of 4 genes NRG1 NRG2 NRG3 and NRG4 respectively The transmembrane forms of neuregulin 1 NRG1 are present within synaptic vesicles including those containing glutamate 6 After exocytosis NRG1 is in the presynaptic membrane where the ectodomain of NRG1 may be cleaved off The ectodomain then migrates across the synaptic cleft and binds to and activates a member of the EGF receptor family on the postsynaptic membrane This has been shown to increase the expression of certain glutamate receptor subunits NRG1 appears to signal for glutamate receptor subunit expression localization and or phosphorylation facilitating subsequent glutamate transmission The NRG1 gene has been identified as a potential gene determining susceptibility to schizophrenia by a combination of genetic linkage and association approaches 6 NRG1 editNRG1 plays a role in synapse development influencing the upregulation of acetylcholine receptor genes beneath the endplate after mammalian motor neurons have made synaptic contact with muscle fibres hence its alternative name ARIA Acetylcholine Receptor Inducing Activity Animal models editA study done on mice in early 2009 has indicated that when neuregulin 1 ErbB signalling is disrupted the dendritic spines of neurons grow but do not fully form This produced no immediate noticeable changes to brain development but in adults there was a reduction of dendritic spines on neurons 7 8 Glutamatergic signalling was markedly disrupted in the mice as a result of the experiment In fish birds and earthworms editNRG 1 2 3 have been found in fish and birds mRNA similar to mammalian Pro NRG2 precursor has been found in humus earthworm Lumbricidae References edit Nagata K Kohda D Hatanaka H et al August 1994 Solution structure of the epidermal growth factor like domain of heregulin alpha a ligand for p180erbB 4 EMBO J 13 15 3517 23 doi 10 1002 j 1460 2075 1994 tb06658 x PMC 395255 PMID 8062828 Vartanian T Fischbach G Miller R 1999 Failure of spinal cord oligodendrocyte development in mice lacking neuregulin Proc Natl Acad Sci U S A 96 2 731 5 Bibcode 1999PNAS 96 731V doi 10 1073 pnas 96 2 731 PMC 15205 PMID 9892702 Yarden Y Burden S 1997 Neuregulins and their receptors a versatile signaling module in organogenesis and oncogenesis Neuron 18 6 847 55 doi 10 1016 S0896 6273 00 80324 4 PMID 9208852 Schroering A Carey DJ 1998 Sensory and motor neuron derived factor is a transmembrane heregulin that is expressed on the plasma membrane with the active domain exposed to the extracellular environment J Biol Chem 273 46 30643 50 doi 10 1074 jbc 273 46 30643 PMID 9804837 Steinthorsdottir V Stefansson H Ghosh S Birgisdottir B Bjornsdottir S Fasquel AC Olafsson O Stefansson K Gulcher JR 2004 Multiple novel transcription initiation sites for NRG1 Gene 342 1 97 105 doi 10 1016 j gene 2004 07 029 PMID 15527969 a b Lemke G Zhou M Ghosh S Harvey RP Gulcher JR Stefansson K Gurney ME Stefansson H Sigurdsson E Steinthorsdottir V Bjornsdottir S Sigmundsson T Brynjolfsson J Gunnarsdottir S Ivarsson O Chou TT Hjaltason O Birgisdottir B Jonsson H Gudnadottir VG Gudmundsdottir E Bjornsson A Ingvarsson B Ingason A Sigfusson S Hardardottir H Lai D Brunner D Mutel V Gonzalo A Sainz J Johannesson G Andresson T Gudbjartsson D Manolescu A Frigge ML Kong A Petursson H 2002 Neuregulin 1 and susceptibility to schizophrenia Am J Hum Genet 71 4 877 892 doi 10 1086 342734 PMC 378543 PMID 12145742 How Microscopic Changes To Brain Cause Schizophrenic Behavior In Mice Barros CS Calabrese B Chamero P Roberts AJ Korzus E Lloyd K Stowers L Mayford M Halpain S Muller U February 2009 Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1 ErbB signaling in the central nervous system Proc Natl Acad Sci U S A 106 11 4507 4512 Bibcode 2009PNAS 106 4507B doi 10 1073 pnas 0900355106 PMC 2657442 PMID 19240213 External links editNeuregulins at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title Neuregulin amp oldid 1193008932, wikipedia, wiki, book, books, library,
