Dual function of Rab1A in secretion and autophagy: hypervariable domain dependence.

Valeriya Gyurkovska, Rakhilya Murtazina, Sarah F Zhao, Sojin Shikano, Yukari Okamoto, Nava Segev

Life science alliance 2023 May

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We currently understand how the different intracellular pathways, secretion, endocytosis, and autophagy are regulated by small GTPases. In contrast, it is unclear how these pathways are coordinated to ensure efficient cellular response to stress. Rab GTPases localize to specific organelles through their hypervariable domain (HVD) to regulate discrete steps of individual pathways. Here, we explored the dual role of Rab1A/B (92% identity) in secretion and autophagy. We show that although either Rab1A or Rab1B is required for secretion, Rab1A, but not Rab1B, localizes to autophagosomes and is required early in stress-induced autophagy. Moreover, replacing the HVD of Rab1B with that of Rab1A enables Rab1B to localize to autophagosomes and regulate autophagy. Therefore, Rab1A-HVD is required for the dual functionality of a single Rab in two different pathways: secretion and autophagy. In addition to this mechanistic insight, these findings are relevant to human health because both the pathways and Rab1A/B were implicated in diseases ranging from cancer to neurodegeneration. © 2023 Gyurkovska et al.

Citation

Valeriya Gyurkovska, Rakhilya Murtazina, Sarah F Zhao, Sojin Shikano, Yukari Okamoto, Nava Segev. Dual function of Rab1A in secretion and autophagy: hypervariable domain dependence. Life science alliance. 2023 May;6(5)