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Title: INPP5K and Atlastin-1 maintain the nonuniform distribution of ER-plasma membrane contacts in neurons
Authors: Sun, Jingbo
Harion, Raihanah
Naito, Tomoki
Saheki, Yasunori
Keywords: Science::Medicine
Issue Date: 2021
Source: Sun, J., Harion, R., Naito, T. & Saheki, Y. (2021). INPP5K and Atlastin-1 maintain the nonuniform distribution of ER-plasma membrane contacts in neurons. Life Science Alliance, 4(11), e202101092-.
Project: MOE2017-T2-2-001 
Journal: Life Science Alliance 
Abstract: 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.
ISSN: 2575-1077
DOI: 10.26508/lsa.202101092
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2021 Sun et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at licenses/by/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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