Research ArticleAmyotrophic Lateral Sclerosis

Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis

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Science Translational Medicine  03 May 2017:
Vol. 9, Issue 388, eaad9157
DOI: 10.1126/scitranslmed.aad9157

Annexing another protein in ALS pathogenesis

Amyotrophic lateral sclerosis (ALS) causes progressive paralysis due to motor neuron degeneration. Smith et al. performed exome sequencing of 751 familial ALS cases and discovered six missense mutations in the ANXA11 gene in 13 individuals, which were absent or vanishingly rare in ~70,000 healthy controls. Abundant annexin 11 protein inclusions were detected in spinal motor neurons and hippocampal axons in a patient with the p.D40G mutation. Annexin 11 is known to play a role in vesicular trafficking between the Golgi and endoplasmic reticulum. Functional studies in transfected cells revealed abnormal binding of mutant annexin 11 to calcyclin, which implicates defective intracellular protein trafficking in ALS pathogenesis.

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