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1 step closer to closure
Date:12/28/2009

Sec24 gene in yeast.

Another gene, Vangl2, when mutated causes remarkably similar defects in spinal closure, so the team set out to see if Vangl2 and Sec24b interact with each other. They first engineered mice to contain mutations in both genes and found that 68 percent of mice had spina bifida and more than half of the mice died within four weeks after birth, strongly suggesting the two genes interact with each other.

Because both proteins are involved in neural tube closure, the team reasoned that perhaps mutations in Sec24b might affect the packaging of Vangl2. Mixing cell components and Vangl2 in a test tube, the team added either Sec24b or other related proteins. Only tubes containing Sec24b were able to package Vangl2; other related proteins could not. The team showed that even small changes in the Vangl2 protein prevented Sec24b from properly sorting Vangl2. Instead, Vangl2 was found clumped inside the cell.

Proper cell patterning, explains Ginty, probably is established with very early stage cellular processes that regulate protein production and transport. And the high prevalence of spina bifida in mice with altered Sec24b and Vangl2 suggests that defects in Sec24b and perhaps other Sec genes might be at the root of spinal cord defects in humans. "It will be interesting to see if that is in fact the case," he says.


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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
Source:Eurekalert

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