Coordination of RAB-8 and RAB-11 during unconventional protein secretion.

Xinxin Li, Bowen Liu, Yue Wen, Jiabin Wang, Yusong R Guo, Anbing Shi, Long Lin

The Journal of cell biology 2024 Feb 05

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Multiple physiology-pertinent transmembrane proteins reach the cell surface via the Golgi-bypassing unconventional protein secretion (UcPS) pathway. By employing C. elegans-polarized intestine epithelia, we recently have revealed that the small GTPase RAB-8/Rab8 serves as an important player in the process. Nonetheless, its function and the relevant UcPS itinerary remain poorly understood. Here, we show that deregulated RAB-8 activity resulted in impaired apical UcPS, which increased sensitivity to infection and environmental stress. We also identified the SNARE VTI-1/Vti1a/b as a new RAB-8-interacting factor involved in the apical UcPS. Besides, RAB-11/Rab11 was capable of recruiting RABI-8/Rabin8 to reduce the guanine nucleotide exchange activity of SMGL-1/GEF toward RAB-8, indicating the necessity of a finely tuned RAB-8/RAB-11 network. Populations of RAB-8- and RAB-11-positive endosomal structures containing the apical UcPS cargo moved toward the apical side. In the absence of RAB-11 or its effectors, the cargo was retained in RAB-8- and RAB-11-positive endosomes, respectively, suggesting that these endosomes are utilized as intermediate carriers for the UcPS. © 2023 Li et al.

Citation

Xinxin Li, Bowen Liu, Yue Wen, Jiabin Wang, Yusong R Guo, Anbing Shi, Long Lin. Coordination of RAB-8 and RAB-11 during unconventional protein secretion. The Journal of cell biology. 2024 Feb 05;223(2)