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nNOSα and nNOSβ localization to aggresome‐like inclusions is dependent on HSP90 activity
Author(s) -
CorsoDíaz Ximena,
Krukoff Teresa L.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06813.x
Subject(s) - hsp90 , aggresome , geldanamycin , microbiology and biotechnology , chemistry , nitric oxide synthase , nitric oxide , neuronal nitric oxide synthase , heat shock protein , chaperone (clinical) , biochemistry , biology , ubiquitin , medicine , organic chemistry , pathology , gene
J. Neurochem. (2010) 114 , 864–872. Abstract Nitric oxide (NO) is a highly reactive gas that participates in many physiological processes including neuroplasticity and neuronal survival. In brain neurons, NO is produced by two variants of neuronal nitric oxide synthase (nNOS), nNOSα and nNOSβ. The activity of nNOSα is tightly regulated at the transcriptional and post‐transcriptional levels. Heat shock protein 90 (HSP90) regulates nNOSα activity by facilitating heme insertion into the nNOSα monomer, resulting in increased NO production. HSP90 also regulates nNOSα degradation through the proteasome pathway. Here, we show in vitro that inhibition of HSP90 with geldanamycin increases nNOS mobility and induces formation of aggresome‐like inclusions containing both nNOSα and nNOSβ in primary cortical neurons. We also report the formation of endogenous nNOS‐containing aggresome‐like inclusions in healthy, untreated, mature primary cortical neurons. We propose that nNOS aggregation may be an additional mechanism for regulating nNOS activity, as has been proposed for inducible nitric oxide synthase. These findings reveal a new role for HSP90 in regulating nNOS sub‐cellular localization and underscore the complexity of nNOS regulatory mechanisms.