Neurofilament protein aggregation in a cell line model system

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Biochem Biophys Res Commun. 2007 Nov 28

Neurofilament protein aggregation in a cell line model system.

Hull E, Spoja C, Cordova M, Cohlberg JA.

Biomedical Sciences Program, Midwestern University, 19555 N. 59th

Avenue, Glendale, AZ 85308, USA.

Protein aggregates are associated with many diseases and even

aggregates of proteins that have no role in disease are inherently

toxic to both neuronal and non-neuronal cells. We have developed a

model system to explore the mechanism of protein aggregation using a

mouse muscle cell line expressing chimeric neurofilament (NF)

proteins, a constituent of the protein aggregates in ALS, Lewy body

dementia, and Charcot-Marie-Tooth disease.

Formation of protein aggregates in these cells leads to reduced cell

viability and activated caspases. Aggregates contained both chimeric

NF proteins and ubiquitin by immunolocalization and were

predominately cytosolic when proteins were expressed at low levels

or for shorter periods of time but were present in the nucleus when

expression levels increased. This system represents a flexible, new

tool to decipher the molecular mechanism of protein aggregation and

the contributions of aggregation to cell toxicity.