Role of phosphorylation on the structural dynamics and function of types III and IV intermediate filaments.
Phosphorylation of types III and IV intermediate filaments (IFs) is known to regulate their organization and function. Phosphorylation of the amino-terminal head domain sites on types III and IV IF proteins plays a key role in the assembly/disassembly of IF subunits into 10 nm filaments, and influences the phosphorylation of sites on the carboxyl-terminal tail domain. These phosphorylation events are largely under the control of second messenger-dependent protein kinases and provide the cells a mechanism to reorganize the IFs in response to the changes in second messenger levels. In mitotic cells, Cdk1, Rho kinase, PAK1 and Aurora-B kinase are believed to regulate vimentin and glial fibrillary acidic protein phosphorylation in a spatio-temporal manner. In neurons, the carboxyl-terminal tail domains of the NF-M and NF-H subunits of heteropolymeric neurofilaments (NFs) are highly phosphorylated by proline-directed protein kinases. The phosphorylation of carboxyl-terminal tail domains of NFs has been suspected to play roles in forming cross-bridges between NFs and microtubules, slowing axonal transport and promoting their integration into cytoskeleton lattice and, in doing so, to control axonal caliber and stabilize the axon. The role of IF phosphorylation in disease pathobiology is discussed.
Sihag
Ram K
RK
Laboratory of Neurochemistry, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Bldg. 49 Room 2A28, MD 20892, USA. RS1950@Verizon.net
Inagaki
Masaki
M
Yamaguchi
Tomoya
T
Shea
Thomas B
TB
Pant
Harish C
HC
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007382:Intermediate Filaments / Q000378:metabolism* / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D021122:Protein Subunits; D014746:Vimentin; D011494:Protein Kinases