Jul 18 – 20, 2022
via Zoom
Asia/Hong_Kong timezone

INPP5K and Atlastin-1 maintain the non-uniform distribution of endoplasmic reticulum-plasma membrane contacts in neuron

Jul 20, 2022, 12:00 PM
6-min slot (4-min talk + 2-min Q&A) Neurobiology Neurobiology & Gene Expression


Raihanah Harion (Nanyang Technological University)


Zoom link: https://hkust.zoom.us/j/93318955512?pwd=bDVqbmk4VGRCTTlhN3VoN0RlMXplZz09
Meeting ID: 933 1895 5512
Passcode: 737042

In neurons, the endoplasmic reticulum (ER) extends throughout all cellular processes, forming multiple contacts with the plasma membrane (PM) to fine-tune neuronal functions. However, the mechanisms that regulate the distribution of neuronal ER-PM contacts remain elusive. In this study, we used the C. elegans DA9 motor neuron to explore the molecular mechanisms that maintain the distribution of neuronal ER-PM contacts. We developed a novel strategy for visualizing ER-PM contacts in live C. elegans neurons using a split GFP approach, and found that neuronal ER-PM contacts are highly enriched in the somatodendritic region and generally absent from the axon. Using a forward genetic screen, we identified that two proteins involved in ER shaping, the dynamin-like GTPase ATLN-1 (human Atlastin-1) and the inositol 5-phosphatase CIL-1 (human INPP5K), help to maintain the non-uniform, somatodendritic enrichment of neuronal ER-PM contacts. Genetic and cell biological assays revealed that CIL-1 acts upstream of ATLN-1 to maintain the balance between tubules and sheets of the ER at cell cortex and restrict the distribution of ER sheets to somatodendrites. In mutants with reduced activities of CIL-1 or ATLN-1, ER sheets expand and invade into the axon. This was accompanied by the ectopic formation of axonal ER-PM contacts and defects in axon regeneration following laser-induced axotomy. Mutations in Atlastin-1 and INPP5K have been linked to various neurological disorders, including hereditary spastic paraplegia and intellectual disability. The unique distribution of neuronal ER-PM contacts maintained by these proteins may support neuronal resilience during the onset and progression of these human disorders.

Primary authors

Raihanah Harion (Nanyang Technological University) Dr Jingbo Sun Dr Tomoki Naito Yasunori Saheki (Nanyang Technological University)

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