Hereditary spastic paraplegia (HSP) is the name given to a group of inherited neurological disorders characterized by progressive stiffness or tightness of the muscles (spasticity) in the lower limbs. Although mutations at over 40 genetic sites have been shown to cause HSP, more than 50% of HSP cases are caused by mutations in one of just three genes: SPG3A, which makes the protein atlastin-1; SPG31, which makes the protein REEP1; and SPG4, which makes the protein spastin.
New research, performed by Craig Blackstone and colleagues, at the NIH, Bethesda, has now determined that a single mechanism is likely to underlie HSP caused by mutations in any of these three genes.
Specifically, the in vitro data generated by Blackstone and colleagues indicate that atlastin-1, spastin, and REEP1 interact within a cellular compartment known as the tubular ER membrane in nerve cells that connect the cerebral cortex of the brain and the spinal cord to coordinate ER shaping and ER interactions with a cellular structure known as the microtubule cytoskeleton and that defects in these processes underlie the more than 50% of HSP cases caused by mutations in SPG3A, SPG31, and SPG4.
The research appears in the Journal of Clinical Investigation.
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