ER stress transforms random olfactory receptor choice into axon targeting precision,Cell

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ER stress transforms random olfactory receptor choice into axon targeting precision
Cell ( IF 45.5 ) Pub Date : 2022-09-26 , DOI: 10.1016/j.cell.2022.08.025
Hani J Shayya ₁ , Jerome K Kahiapo ₂ , Rachel Duffié ₃ , Katherine S Lehmann ₄ , Lisa Bashkirova ₃ , Kevin Monahan ₃ , Ryan P Dalton ₅ , Joanna Gao ₆ , Song Jiao ₄ , Ira Schieren ₃ , Leonardo Belluscio ₄ , Stavros Lomvardas ₇

Affiliation

Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY 10027, USA; Medical Scientist Training Program, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY 10027, USA; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY 10027, USA.
Developmental Neural Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
The Miller Institute for Basic Research in Science, University of California, Berkeley, Berkeley, CA 94720, USA.
Barnard College, New York, NY 10025, USA.
Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Neuroscience, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Olfactory sensory neurons (OSNs) convert the stochastic choice of one of >1,000 olfactory receptor (OR) genes into precise and stereotyped axon targeting of OR-specific glomeruli in the olfactory bulb. Here, we show that the PERK arm of the unfolded protein response (UPR) regulates both the glomerular coalescence of like axons and the specificity of their projections. Subtle differences in OR protein sequences lead to distinct patterns of endoplasmic reticulum (ER) stress during OSN development, converting OR identity into distinct gene expression signatures. We identify the transcription factor Ddit3 as a key effector of PERK signaling that maps OR-dependent ER stress patterns to the transcriptional regulation of axon guidance and cell-adhesion genes, instructing targeting precision. Our results extend the known functions of the UPR from a quality-control pathway that protects cells from misfolded proteins to a sensor of cellular identity that interprets physiological states to direct axon wiring.

中文翻译：

内质网应激将随机嗅觉受体选择转化为轴突靶向精度

嗅觉感觉神经元 (OSN) 将超过 1,000 个嗅觉受体 (OR) 基因之一的随机选择转化为针对嗅球中 OR 特异性肾小球的精确且定型的轴突。在这里，我们证明未折叠蛋白反应（UPR）的 PERK 臂调节类似轴突的肾小球聚结及其投影的特异性。 OR 蛋白序列的细微差异导致 OSN 发育过程中内质网 (ER) 应激的不同模式，将 OR 同一性转化为不同的基因表达特征。我们将转录因子Ddit3确定为 PERK 信号传导的关键效应器，将 OR 依赖性 ER 应激模式映射到轴突引导和细胞粘附基因的转录调节，指示靶向精度。我们的研究结果将 UPR 的已知功能从保护细胞免受错误折叠蛋白质影响的质量控制途径扩展到解释生理状态以指导轴突接线的细胞身份传感器。

更新日期：2022-09-26

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