The protein is also critical for maintaining the network of "microtubules" that constitutes the transport system for proteins to different parts of the cell, he added. Such cellular transport is particularly important in the peripheral nerves given that neurons must span the distance from the spinal cord to the feet and hands, Vance said.
Further study revealed that the defects in the dynamin 2 gene all fell in the region that encodes the same portion of its product protein. Two of the families, who carried a mutation that altered the same amino acid building block of the dynamin 2 protein, also shared a deficiency of white blood cells, a condition not previously linked to CMT, the researchers reported.
To further explore the effect of the mutations, the researchers inserted dynamin 2 with the particular defects into cultured cells. Cells with the mutant dynamin gene exhibited abnormalities, including disorganization of the microtubule network and an inability to take up substances through endocytosis. Endocytosis is a process whereby the cell membrane engulfs materials, forming sacs that are then internalized by the cell.
"Dynamin 2 represents the third protein causing CMT that contains a domain related to the fusion of cell membranes, suggesting an exceptional role for these pathways for CMT and for nervous system diseases in general," Zchner said. Zchner, Vance and their colleagues reported last year that the gene mitofusin 2, which plays a critical role in the fusion and fission of the cellular powerhouses known as mitochondria, underlies CMT type 2A.
While the study results provide intriguing evidence that defects in microtubule organization and endocytosis might underlie the symptoms of intermediate CMT, further examination of the gene's effects will be required given its broad variety of cellular functions, Vance said. Further work is also required to discern the role of dynamin 2 in the development or
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-660-1306
Duke University Medical Center
31-Jan-2005