TY - JOUR T1 - Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins JF - bioRxiv DO - 10.1101/069005 SP - 069005 AU - Belgin Yalçın AU - Lu Zhao AU - Martin Stofanko AU - Niamh C O’Sullivan AU - Zi Han Kang AU - Annika Roost AU - Matthew R. Thomas AU - Sophie Zaessinger AU - Olivier Blard AU - Alex L. Patto AU - Valentina Baena AU - Mark Terasaki AU - Cahir J O’Kane Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/12/01/069005.abstract N2 - Axons contain an endoplasmic reticulum (ER) network that is largely smooth and tubular, thought to be continuous with ER throughout the neuron, and distinct in form and function from rough ER; the mechanisms that form this continuous network in axons are not well understood. Mutations affecting proteins of the reticulon or REEP families, which contain intramembrane hairpin domains that can model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). Here, we show that these proteins are required for modeling the axonal ER network in Drosophila. Loss of reticulon or REEP proteins can lead to expansion of ER sheets, and to partial loss of ER from distal motor axons. Ultrastructural analysis reveals an extensive ER network in every axon of peripheral nerves, which is reduced in larvae that lack reticulon and REEP proteins, with defects including larger and fewer tubules, and occasional gaps in the ER network, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of the axonal ER network, suggesting an important role for ER modeling in axon maintenance and function. ER -