Milano Samantha N, Bayer Livia V, Ko Julie J, Casella Caroline E, Bratu Diana P
Department of Biological Sciences, Hunter College, City University of New York, NY, 10065 USA.
Program in Molecular, Cellular, and Developmental Biology, The Graduate Center, City University of New York, NY, 10016 USA.
bioRxiv. 2024 Jul 5:2024.07.03.601952. doi: 10.1101/2024.07.03.601952.
Processing bodies (P-bodies) are cytoplasmic membrane-less organelles which host multiple mRNA processing events. While the fundamental principles of P-body organization are beginning to be elucidated , a nuanced understanding of how their assembly is regulated remains elusive. Here, we investigate the potential link between ER exit sites and P-bodies in egg chambers. Employing a combination of live and super-resolution imaging, we found that P-bodies associated with ER exit sites are larger and less mobile than cytoplasmic P-bodies, indicating that they constitute a distinct class of P-bodies which are more mature than their cytoplasmic counterparts. Moreover, we demonstrate that altering the composition of ER exit sites has differential effects on core P-body proteins (Me31B, Cup, and Trailer Hitch) suggesting a potential role for ER exit sites in P-body organization. We further show that in the absence of ER exit sites, P-body integrity is compromised and the stability and translational repression efficiency of the maternal mRNA, , are reduced. Finally, we show that ER stress is communicated to P-bodies via ER exit sites, highlighting the pivotal role of ER exit sites as a bridge between membrane-bound and membrane-less organelles in ER stress response. Together, our data unveils the significance of ER exit sites not only in governing P-body organization, but also in facilitating inter-organellar communication during stress, potentially bearing implications for a variety of disease pathologies.
加工小体（P小体）是细胞质中无膜细胞器，承载多种mRNA加工事件。虽然P小体组织的基本原理开始得到阐明，但对其组装如何受到调控的细微理解仍然难以捉摸。在这里，我们研究了卵室中内质网出口位点与P小体之间的潜在联系。通过结合活细胞成像和超分辨率成像，我们发现与内质网出口位点相关的P小体比细胞质中的P小体更大且移动性更低，这表明它们构成了一类独特的P小体，比细胞质中的P小体更成熟。此外，我们证明改变内质网出口位点的组成对核心P小体蛋白（Me31B、Cup和Trailer Hitch）有不同影响，这表明内质网出口位点在P小体组织中可能发挥作用。我们进一步表明，在内质网出口位点缺失的情况下，P小体的完整性受到损害，母体mRNA的稳定性和翻译抑制效率降低。最后，我们表明内质网应激通过内质网出口位点传递到P小体，突出了内质网出口位点作为内质网应激反应中膜结合细胞器和无膜细胞器之间桥梁的关键作用。总之，我们的数据揭示了内质网出口位点不仅在控制P小体组织方面的重要性，而且在应激期间促进细胞器间通讯方面的重要性，这可能对多种疾病病理产生影响。
