Regulation of inducible nitric oxide synthase by aggresome formation.
Misfolding and aggregation of proteins play an important part in the pathogenesis of several genetic and degenerative diseases. Recent evidence suggests that cells have evolved a pathway that involves sequestration of aggregated proteins into specialized "holding stations" called aggresomes. Here we show that cells regulate inducible NO synthase (iNOS), an important host defense protein, through aggresome formation. iNOS aggresome formation depends on a functional dynein motor and the integrity of the microtubules. The iNOS aggresome represents a "physiologic aggresome" and thus defines a new paradigm for cellular regulation of protein processing. This study indicates that aggresome formation in response to misfolded proteins may merely represent an acceleration of an established physiologic regulatory process for specific proteins whose regulation by aggresome formation is deemed necessary by the cell.
Kolodziejska
Katarzyna E
KE
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Burns
Alan R
AR
Moore
Robert H
RH
Stenoien
David L
DL
Eissa
N Tony
NT
D000818:Animals; D002478:Cells, Cultured; D004398:Dyneins / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D049452:Green Fluorescent Proteins; D006801:Humans; D007091:Image Processing, Computer-Assisted; D002479:Inclusion Bodies / Q000187:drug effects / Q000378:metabolism*; D007211:Indoles; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D008854:Microscopy, Electron; D022101:Microtubule-Organizing Center / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D015739:Nocodazole / Q000494:pharmacology
D007211:Indoles; D007976:Leupeptins; D049452:Green Fluorescent Proteins; C007293:DAPI; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D004398:Dyneins; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D015739:Nocodazole