ArticleMolecular biology of the cell2007
The extracellular linker of pro-neuregulin-alpha2c is required for efficient sorting and juxtacrine function.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 24 citations in OpenAlex.
- Neuregulin-1/ErbB4 upregulates acetylcholine receptors via Akt/mTOR/p70S6K: a study in a rat model of obstetric brachial plexus palsy andActa biochimica et biophysica Sinica · 2022Article
- PDCD4 limits prooncogenic neuregulin-ErbB signaling.Cellular and molecular life sciences : CMLS · 2021Article
- MiRNAs, lncRNAs, and circular RNAs as mediators in hypertension-related vascular smooth muscle cell dysfunction.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Review
- The immunoglobulin-like domain of neuregulins potentiates ErbB3/HER3 activation and cellular proliferation.Molecular oncology · 2018Article
- Article
- Neuregulin 1 expression and electrophysiological abnormalities in the Neuregulin 1 transmembrane domain heterozygous mutant mouse.PloS one · 2015Article
- Neuregulin-1 signalling and antipsychotic treatment: potential therapeutic targets in a schizophrenia candidate signalling pathway.Psychopharmacology · 2013Review
- Transautocrine signaling by membrane neuregulins requires cell surface targeting, which is controlled by multiple domains.The Journal of biological chemistry · 2011Article
- P-Rex1 participates in Neuregulin-ErbB signal transduction and its expression correlates with patient outcome in breast cancer.Oncogene · 2011Article
- Neuregulin 1 in neural development, synaptic plasticity and schizophrenia.Nature reviews. Neuroscience · 2008Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuregulins (NRGs) play important roles in animal physiology, and their disregulation has been linked to diseases such as cancer or schizophrenia. The NRGs may be produced as transmembrane proteins (proNRGs), even though they lack an N-terminal signal sequence. This raises the question of how NRGs are sorted to the plasma membrane. It is also unclear whether in their transmembrane state, the NRGs are biologically active. During studies aimed at solving these questions, we found that deletion of the extracellular juxtamembrane region termed the linker, decreased cell surface exposure of the mutant proNRG(DeltaLinker), and caused its entrapment at the cis-Golgi. We also found that cell surface-exposed transmembrane NRG forms retain biological activity. Thus, a mutant whose cleavage is impaired but is correctly sorted to the plasma membrane activated ErbB receptors in trans and also stimulated proliferation. Because the linker is implicated in surface sorting and the regulation of the cleavage of transmembrane NRGs, our data indicate that this region exerts multiple important roles in the physiology of NRGs.
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