Hanieh Falahati, Yumei Wu, Mumu Fang, Pietro De Camilli
{"title":"Ectopic reconstitution of a spine-apparatus-like structure provides insight into mechanisms underlying its formation.","authors":"Hanieh Falahati, Yumei Wu, Mumu Fang, Pietro De Camilli","doi":"10.1016/j.cub.2024.11.010","DOIUrl":null,"url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) is a continuous cellular endomembrane network that displays focal specializations. Most notable examples of such specializations include the spine apparatus of neuronal dendrites and the cisternal organelle of axonal initial segments. Both organelles exhibit stacks of smooth ER sheets with a narrow lumen, interconnected by a dense protein matrix. The actin-binding protein synaptopodin is required for their formation, but the underlying mechanisms remain unknown. Here, we report that the spine apparatus and synaptopodin are conserved from flies to mammals and that a highly conserved region of this protein is necessary, but not sufficient, for its association with ER. We reveal a dual role of synaptopodin in generating actin bundles and in linking them to the ER. Expression of a synaptopodin construct constitutively anchored to the ER in non-neuronal cells is sufficient to generate stacked ER cisterns resembling the spine apparatus. Cisterns within these stacks are molecularly distinct from the surrounding ER and are connected to each other by an actin-based matrix that contains proteins also found at the spine apparatus of neuronal spines. Our findings shed light on mechanisms governing the biogenesis of this peculiar structure and represent a step toward understanding the elusive properties of this organelle.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":""},"PeriodicalIF":8.1000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cub.2024.11.010","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The endoplasmic reticulum (ER) is a continuous cellular endomembrane network that displays focal specializations. Most notable examples of such specializations include the spine apparatus of neuronal dendrites and the cisternal organelle of axonal initial segments. Both organelles exhibit stacks of smooth ER sheets with a narrow lumen, interconnected by a dense protein matrix. The actin-binding protein synaptopodin is required for their formation, but the underlying mechanisms remain unknown. Here, we report that the spine apparatus and synaptopodin are conserved from flies to mammals and that a highly conserved region of this protein is necessary, but not sufficient, for its association with ER. We reveal a dual role of synaptopodin in generating actin bundles and in linking them to the ER. Expression of a synaptopodin construct constitutively anchored to the ER in non-neuronal cells is sufficient to generate stacked ER cisterns resembling the spine apparatus. Cisterns within these stacks are molecularly distinct from the surrounding ER and are connected to each other by an actin-based matrix that contains proteins also found at the spine apparatus of neuronal spines. Our findings shed light on mechanisms governing the biogenesis of this peculiar structure and represent a step toward understanding the elusive properties of this organelle.
期刊介绍:
Current Biology is a comprehensive journal that showcases original research in various disciplines of biology. It provides a platform for scientists to disseminate their groundbreaking findings and promotes interdisciplinary communication. The journal publishes articles of general interest, encompassing diverse fields of biology. Moreover, it offers accessible editorial pieces that are specifically designed to enlighten non-specialist readers.