title: Atlastin regulates store-operated calcium entry for nerve growth factor-induced neurite outgrowth.
abstract: Homotypic membrane fusion of the endoplasmic reticulum (ER) is mediated by a class of dynamin-like GTPases known as atlastin (ATL). Depletion of or mutations in ATL cause an unbranched ER morphology and hereditary spastic paraplegia (HSP), a neurodegenerative disease characterized by axon shortening in corticospinal motor neurons and progressive spasticity of the lower limbs. How ER shaping is linked to neuronal defects is poorly understood. Here, we show that dominant-negative mutants of ATL1 in PC-12 cells inhibit nerve growth factor (NGF)-induced neurite outgrowth. Overexpression of wild-type or mutant ATL1 or depletion of ATLs alters ER morphology and affects store-operated calcium entry (SOCE) by decreasing STIM1 puncta formation near the plasma membrane upon calcium depletion of the ER. In addition, blockage of the STIM1-Orai pathway effectively abolishes neurite outgrowth of PC-12 cells stimulated by NGF. These results suggest that SOCE plays an important role in neuronal regeneration, and mutations in ATL1 may cause HSP, partly by undermining SOCE.
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, and Tianjin Key Laboratory of Protein Sciences, Tianjin 300071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Temple, Texas, USA.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Si
authors.affiliation: Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Temple, Texas, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Temple, Texas, USA.
authors.forename: Shenyuan L
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D000071446:Neuronal Outgrowth / Q000187:drug effects / Q000235:genetics; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C502240:NGF protein, human; D020932:Nerve Growth Factor; C440006:ATL1 protein, human; D019204:GTP-Binding Proteins; D002118:Calcium