A Cysteine-Rich Isoform of Neuregulin Controls the Level of Expression of Neuronal Nicotinic Receptor Channels during Synaptogenesis
نویسندگان
چکیده
We report here that neuregulin (NRG) isoforms with a conserved cysteine-rich domain (CRD) in their N terminus regulate expression of nicotinic acetylcholine receptors (nAChRs) at developing interneuronal synapses and report the isolation of transmembrane NRG isoforms with this CRD within the N-terminal portion. CRD-NRG mRNA and immunoreactive protein are detected early in developing presynaptic (visceral motor) neurons. The levels of expression of CRD-NRG peak prior to the formation of synapses with their postsynaptic partners, the ganglionic sympathetic neurons. Recombinant CRD-NRG mimics the effects of presynaptic input on target neurons. Functional deletion of CRD-NRG from presynaptic neurons abolishes the upregulation of nAChR expression induced by input-derived soluble material. Thus, CRD-NRG appears to be both a necessary and a sufficient signal for the control of neuronal nAChR expression during synaptogenesis.
منابع مشابه
The Effect of Swimming Endurance Exercise on Cell Death and Nicotinic Acetylcholine Receptor Gene Expression in Brain of Rat: An Experimental Study of Alzheimer's Disease Model
Background and Objectives: Alzheimerchr('39')s disease (AD) is a neurodegenerative disease which is marked by impaired cholinergic function and decreased nicotinic acetylcholine receptor (nAChRs) density. nAChRs are important mediators of cholinergic signaling in modulation of learning and memory function. In Alzheimer hippocampus is particularly vulnerable to specific degenerative processes an...
متن کاملCysteine-Rich Domain Isoforms of the Neuregulin-1 Gene Are Required for Maintenance of Peripheral Synapses
Neuregulin-1 (NRG-1) signaling has been implicated in inductive interactions between pre- and postsynaptic partners during synaptogenesis. We used gene targeting to selectively disrupt cysteine-rich domain-(CRD-) containing NRG-1 isoforms. In CRD-NRG-1-/-mice, peripheral projections defasciculated and displayed aberrant branching patterns within their targets. Motor nerve terminals were transie...
متن کاملDysregulated expression of neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity.
Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyze...
متن کاملNeuregulin Upregulates Microglial α7 Nicotinic Acetylcholine Receptor Expression in Immortalized Cell Lines: Implications for Regulating Neuroinflammation
Neuregulin, previously known as ARIA, is a signaling protein involved in cell survival, synaptic plasticity, cell communication and differentiation. Neuregulin has also been described as a potent inducer of acetylcholine receptor transcription in muscle and although both neuregulin and acetylcholine have been individually described to have neuroprotective roles, their relationship in the cholin...
متن کاملNeuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro.
Neuregulin 1 (Nrg-1) isoforms have been shown to influence the emergence and growth of oligodendrocytes, the CNS myelin-forming cells. We have investigated how Nrg-1 signaling of ErbB receptors specifically controls the early stages of oligodendrocyte generation from multipotential neural precursors (NPs). We show here that embryonic striatal NPs express multiple Nrg-1 transcripts and proteins ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Neuron
دوره 20 شماره
صفحات -
تاریخ انتشار 1998