Identification of Neuregulin-2 as a novel stress granule component

Abstract

Stress Granules (SGs) are microscopically visible, phase dense aggregates of translationally stalled messenger ribonucleoprotein (mRNP) complexes formed in response to distinct stress conditions. It is generally considered that SG formation is induced to protect cells from conditions of stress. The precise constituents of SGs and the mechanism through which SGs are dynamically regulated in response to stress are not completely understood. Hence, it is important to identify proteins which regulate SG assembly and disassembly. In the present study, we report Neuregulin-2 (NRG2) as a novel component of SGs; furthermore, depletion of NRG2 potently inhibits SG formation. We also demonstrate that NRG2 specifically localizes to SGs under various stress conditions. Knockdown of NRG2 has no effect on stress-induced polysome disassembly, suggesting that the component does not influence early step of SG formation. It was also observed that reduced expression of NRG2 led to marginal increase in cell survival under arsenite-induced stress. [BMB Reports 2016; 49(8): 449-454]

Using Machine Intelligence to Uncover Alzheimer’s Disease Progression Heterogeneity

“…Interestingly, there appears to be a network between TUBB1, ASB4, and PDE5A, suggesting that Class I represents a subpopulation defined by regulation of vasculogenesis (Figure 2) [33][34][35]. plasticity [37,38]. ZNF3 is a zinc-finger protein that is differentially expressed in AD and is involved in cell differentiation and proliferation [39].…”

“…by NRG2 and ZNF3. Neuregulins (NRGs) are a member of epidermal growth factor (EGF)-related proteins, which stimulate ErbB-receptor tyrosine phosphorylation that elicits different downstream signaling pathways such as MAPK, PI3, PKC, and JAK-STAT pathways and are associated with synaptic plasticity [37,38]. Neuregulin-2 (Nrg2) dysregulation has been associated with cancer, schizophrenia, and AD [37].…”

Molecular Mechanisms Linking ALS/FTD and Psychiatric Disorders, the Potential Effects of Lithium

“…Even genes and proteins which are associated with bipolar disorder converge on UPR-related pathways controlling translation initiation and RNA processing (Carter, 2007; Darby et al, 2016; Laguesse and Ron, 2019). For instance, disrupted in schizophrenia 1 (DISC1) and neuregulin (NRG), which are implicated synaptic alterations and defective cytoskeleton-related organelle transport, induce eIF3-dependent SG assembly in response to environmental stressors (Ogawa et al, 2005; Kim J.A. et al, 2016).…”

“…et al, 2016). NRG2 also localizes to SGs, and depletion of NRG2 inhibits SG aggregation to promote cell survival during ER stress (Kim J.A. et al, 2016).…”

Neuregulin in Health and Disease

“…There are few studies that describe NRG-2, −3 and −4 and a complete analysis of their function remains a challenge. However, NRG-2 was recently reported as a component of stress granules (SG), microscopically visible aggregates of translationally stalled messenger ribonucleoprotein complexes that are formed in response to direct stress conditions [2]. Furthermore, it was shown that NRG-2, secreted from astrocytes, bound to ErbB3 on neurons and promoted neuronal survival [3].…”