TY - JOUR T1 - INPP5K and Atlastin-1 maintain the nonuniform distribution of ER–plasma membrane contacts in neurons JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101092 VL - 4 IS - 11 SP - e202101092 AU - Jingbo Sun AU - Raihanah Harion AU - Tomoki Naito AU - Yasunori Saheki Y1 - 2021/11/01 UR - https://www.life-science-alliance.org/content/4/11/e202101092.abstract N2 - In neurons, the ER extends throughout all cellular processes, forming multiple contacts with the plasma membrane (PM) to fine-tune neuronal physiology. However, the mechanisms that regulate the distribution of neuronal ER-PM contacts are not known. Here, we used the Caenorhabditis elegans DA9 motor neuron as our model system and found that neuronal ER-PM contacts are enriched in soma and dendrite and mostly absent in axons. Using forward genetic screen, we identified that the inositol 5-phosphatase, CIL-1 (human INPP5K), and the dynamin-like GTPase, ATLN-1 (human Atlastin-1), help to maintain the non-uniform, somatodendritic enrichment of neuronal ER-PM contacts. Mechanistically, CIL-1 acts upstream of ATLN-1 to maintain the balance between ER tubules and sheets. In mutants of CIL-1 or ATLN-1, ER sheets expand and invade into the axon. This is accompanied by the ectopic formation of axonal ER-PM contacts and defects in axon regeneration following laser-induced axotomy. As INPP5K and Atlastin-1 have been linked to neurological disorders, the unique distribution of neuronal ER-PM contacts maintained by these proteins may support neuronal resilience during the onset and progression of these diseases. ER -