Department of Medical and Biological Sciences, The Catholic University of Korea, Gyeonggi-Do, Bucheon, 14662, South Korea.
Department of Biotechnology, The Catholic University of Korea, Gyeonggi-Do, Bucheon, 14662, South Korea.
Mol Brain. 2024 Sep 2;17(1):63. doi: 10.1186/s13041-024-01132-3.
ATG9A is the only integral membrane protein among core autophagy-related (ATG) proteins. We previously found that ATG9A does not co-assemble into synaptophysin-positive vesicles, but rather, localizes to a distinct pool of vesicles within synapsin condensates in both fibroblasts and nerve terminals. The endocytic origin of these vesicles further suggests the existence of different intracellular sorting or segregation mechanisms for ATG9A and synaptophysin in cells. However, the precise underlying mechanism remains largely unknown. In this follow-up study, we investigated the endosomal localization of these two proteins by exploiting the advantages of a Rab5 mutant that induces the formation of enlarged endosomes. Notably, ATG9A and synaptophysin intermix perfectly and do not segregate on giant endosomes, indicating that the separation of these two proteins is not solely caused by the inherent properties of the proteins, but possibly by other unknown factors.
ATG9A 是唯一一种核心自噬相关（ATG）蛋白中的完整膜蛋白。我们之前发现，ATG9A 不会与突触小泡蛋白阳性囊泡共同组装，而是定位于成纤维细胞和神经末梢中突触小泡蛋白凝聚物中的一个独特囊泡池。这些囊泡的内吞起源进一步表明，在细胞中 ATG9A 和突触小泡蛋白可能存在不同的细胞内分拣或隔离机制。然而，确切的潜在机制在很大程度上仍然未知。在这项后续研究中，我们通过利用一种 Rab5 突变体的优势来研究这两种蛋白的内体定位，该突变体诱导形成扩大的内体。值得注意的是，ATG9A 和突触小泡蛋白完美混合，在内体上不分离，表明这两种蛋白的分离不是仅由蛋白质的固有特性引起的，而是可能由其他未知因素引起的。
