Editors' ChoiceCell Biology

Not making the right contacts

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Science  05 May 2017:
Vol. 356, Issue 6337, pp. 498-499
DOI: 10.1126/science.356.6337.498-b

The microtubule-severing enzyme spastin is mutated in the inherited neural disease, or axonopathy, called hereditary spastic paraplegia (HSP). The endoplasmic reticulum (ER) within cells, including neurons, plays a role in defining the position and timing of endosomal tubule fission. Allison et al. identified a role for spastin at ER-endosome contact sites during endosomal tubule fission. Failure of this process caused problems in lysosomal enzyme trafficking. Lysosomal abnormalities developed in primary cortical neurons from a spastin-HSP mouse model, human stem cell–derived neurons from a spastin-HSP patient, and neurons from mice lacking the ER-shaping protein REEP1. All of these neurons developed pathological axonal swellings associated with accumulations of abnormal lysosomes. Failure to correctly manage lysosome biogenesis may play a role in multiple HSPs and possibly other neurodegenerative conditions.

J. Cell Biol. 10.1083/jcb201609033 (2017).

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