Matches in SemOpenAlex for { <https://semopenalex.org/work/W1992833530> ?p ?o ?g. }
- W1992833530 endingPage "1260" @default.
- W1992833530 startingPage "1251" @default.
- W1992833530 abstract "Neuregulin1 (NRG1) is a single transmembrane protein that plays a critical role in neural development and synaptic plasticity. Both NRG1 and its receptor, ErbB4, are well-established risk genes of schizophrenia. The NRG1 ecto-domain (ED) binds and activates ErbB4 following proteolytic cleavage of pro-NRG1 precursor protein. Although several studies have addressed the function of NRG1 in brain, very little is known about the cleavage and shedding mechanism. Here we show that the neuronal vesicular protein calcyon is a potent activator and key determinant of NRG1 ED cleavage and shedding. Calcyon stimulates clathrin-mediated endocytosis and endosomal targeting; and its levels are elevated in postmortem brains of schizophrenics. Overexpression of calcyon stimulates NRG1 cleavage and signaling in vivo, and as a result, GABA transmission is enhanced in calcyon overexpressing mice. Conversely, NRG1 cleavage, ErbB4 activity and GABA transmission are decreased in calcyon null mice. Moreover, stimulation of NRG1 cleavage by calcyon was recapitulated in HEK 293 cells suggesting the mechanism involved is cell-autonomous. Finally, studies with site-specific mutants in calcyon and inhibitors for the major sheddases indicate that the stimulatory effects of calcyon on NRG1 cleavage and shedding depend on clathrin-mediated endocytosis, β-secretase 1, and interaction with clathrin adaptor proteins. Together these results identify a novel mechanism for NRG1 cleavage and shedding." @default.
- W1992833530 created "2016-06-24" @default.
- W1992833530 creator A5001143507 @default.
- W1992833530 creator A5023650604 @default.
- W1992833530 creator A5025921043 @default.
- W1992833530 creator A5033436760 @default.
- W1992833530 creator A5037381593 @default.
- W1992833530 creator A5037736308 @default.
- W1992833530 creator A5038122409 @default.
- W1992833530 creator A5053375725 @default.
- W1992833530 creator A5076501435 @default.
- W1992833530 creator A5077054573 @default.
- W1992833530 creator A5083041006 @default.
- W1992833530 date "2014-10-28" @default.
- W1992833530 modified "2023-10-17" @default.
- W1992833530 title "Calcyon stimulates neuregulin 1 maturation and signaling" @default.
- W1992833530 cites W1502026371 @default.
- W1992833530 cites W1546204865 @default.
- W1992833530 cites W1549817168 @default.
- W1992833530 cites W1851262442 @default.
- W1992833530 cites W1949229324 @default.
- W1992833530 cites W1964921208 @default.
- W1992833530 cites W1967680221 @default.
- W1992833530 cites W1976782226 @default.
- W1992833530 cites W1980165830 @default.
- W1992833530 cites W1980276310 @default.
- W1992833530 cites W1982135531 @default.
- W1992833530 cites W1984418618 @default.
- W1992833530 cites W1989453114 @default.
- W1992833530 cites W1991981632 @default.
- W1992833530 cites W1993447350 @default.
- W1992833530 cites W1993895538 @default.
- W1992833530 cites W1998094731 @default.
- W1992833530 cites W1999242469 @default.
- W1992833530 cites W2011424005 @default.
- W1992833530 cites W2013995451 @default.
- W1992833530 cites W2015760775 @default.
- W1992833530 cites W2016016539 @default.
- W1992833530 cites W2016717347 @default.
- W1992833530 cites W2018912242 @default.
- W1992833530 cites W2019007281 @default.
- W1992833530 cites W2019016101 @default.
- W1992833530 cites W2019184486 @default.
- W1992833530 cites W2019203795 @default.
- W1992833530 cites W2020237866 @default.
- W1992833530 cites W2023527463 @default.
- W1992833530 cites W2031755128 @default.
- W1992833530 cites W2036146366 @default.
- W1992833530 cites W2038661578 @default.
- W1992833530 cites W2042089915 @default.
- W1992833530 cites W2042124706 @default.
- W1992833530 cites W2042190017 @default.
- W1992833530 cites W2043467783 @default.
- W1992833530 cites W2044515352 @default.
- W1992833530 cites W2047560376 @default.
- W1992833530 cites W2047568471 @default.
- W1992833530 cites W2052571439 @default.
- W1992833530 cites W2062820112 @default.
- W1992833530 cites W2066499240 @default.
- W1992833530 cites W2070347840 @default.
- W1992833530 cites W2070423416 @default.
- W1992833530 cites W2072101304 @default.
- W1992833530 cites W2075935381 @default.
- W1992833530 cites W2082919360 @default.
- W1992833530 cites W2083062984 @default.
- W1992833530 cites W2084918432 @default.
- W1992833530 cites W2085494041 @default.
- W1992833530 cites W2094560840 @default.
- W1992833530 cites W2094970290 @default.
- W1992833530 cites W2097333356 @default.
- W1992833530 cites W2103905237 @default.
- W1992833530 cites W2106584815 @default.
- W1992833530 cites W2112032807 @default.
- W1992833530 cites W2112927743 @default.
- W1992833530 cites W2121801466 @default.
- W1992833530 cites W2123788299 @default.
- W1992833530 cites W2123941817 @default.
- W1992833530 cites W2124421908 @default.
- W1992833530 cites W2125705356 @default.
- W1992833530 cites W2129955844 @default.
- W1992833530 cites W2136903466 @default.
- W1992833530 cites W2139140006 @default.
- W1992833530 cites W2144034070 @default.
- W1992833530 cites W2157860584 @default.
- W1992833530 cites W2161641617 @default.
- W1992833530 cites W2161820433 @default.
- W1992833530 cites W2164774934 @default.
- W1992833530 cites W2165068126 @default.
- W1992833530 cites W2167693778 @default.
- W1992833530 cites W2168801997 @default.
- W1992833530 cites W2810778905 @default.
- W1992833530 cites W4234358442 @default.
- W1992833530 doi "https://doi.org/10.1038/mp.2014.131" @default.
- W1992833530 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25349163" @default.
- W1992833530 hasPublicationYear "2014" @default.
- W1992833530 type Work @default.
- W1992833530 sameAs 1992833530 @default.
- W1992833530 citedByCount "13" @default.