Developmental Cell ( IF 10.7 ) Pub Date : 2023-12-05 , DOI: 10.1016/j.devcel.2023.11.006 Jiaqi Sun 1 , Yang Shao 2 , Songyang Wang 2 , Xunzheng Li 2 , Shuqing Feng 2 , Weina Wang 3 , Pierre Leroy 3 , Chengyang Li 4 , Huanquan Zheng 3
The expansion of autophagosomes requires a controlled association with the endoplasmic reticulum (ER). However, the mechanisms governing this process are not well defined. In plants, ATG18a plays a key role in autophagosome formation in response to stress, yet the factors regulating the process are unknown. This study finds that ATG18a acts as a downstream effector of RABC1, a member of the poorly characterized Rab18/RabC GTPase subclass in plants. Active RABC1 interacts with ATG18a on the ER, particularly under nutrient starvation. In rabc1 mutants, autophagy is compromised, especially under nutrient deprivation, affecting the ER association and expansion of ATG18a-positive autophagosomes. Furthermore, both dominant-negative and constitutively active RABC1 forms inhibit autophagy. The dominant inactive RABC1 impedes the ER association of ATG18a, whereas the constitutively active RABC1 delays ATG18a detachment from the ER. Collectively, RABC1 regulates the ER association and the subsequent detachment of ATG18a-positive autophagosomes during nutrient starvation.
中文翻译:
拟南芥 Rab18 GTPase 通过将 ATG18a 束缚到 ER 来响应营养饥饿,从而促进自噬
自噬体的扩张需要与内质网 (ER) 的受控关联。然而,控制这一过程的机制尚未明确定义。在植物中,ATG18a 在响应应激的自噬体形成中发挥着关键作用,但调节该过程的因素尚不清楚。这项研究发现 ATG18a 充当 RABC1 的下游效应子,RABC1 是植物中特征不明的 Rab18/RabC GTPase 亚类的成员。活跃的 RABC1 与 ER 上的 ATG18a 相互作用,特别是在营养匮乏的情况下。在rabc1突变体中,自噬受到损害,尤其是在营养缺乏的情况下,影响 ER 关联和 ATG18a 阳性自噬体的扩张。此外,显性失活和组成型活性 RABC1 形式都会抑制自噬。显性失活的 RABC1 阻碍 ATG18a 与 ER 的结合,而组成型活性的 RABC1 则延迟 ATG18a 从 ER 的分离。总的来说,RABC1 调节 ER 关联以及随后营养饥饿期间 ATG18a 阳性自噬体的分离。