Calpain mobilizes Atg9/Bif-1 vesicles from Golgi stacks upon autophagy induction by thapsigargin

Marcassa, Elena, Raimondi, Marzia, Anwar, Tahira, Eskelinen, Eeva-Liisa, Myers, Michael P, Triolo, Gianluca, Schneider, Claudio and Demarchi, Francesca (2017) Calpain mobilizes Atg9/Bif-1 vesicles from Golgi stacks upon autophagy induction by thapsigargin. BIOLOGY OPEN, 6 (5). pp. 551-562.

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Abstract

CAPNS1 is essential for stability and function of the ubiquitous calcium-dependent proteases micro- and milli-calpain. Upon inhibition of the endoplasmic reticulum Ca²⁺ ATPase by 100 nM thapsigargin, both micro-calpain and autophagy are activated in human U2OS osteosarcoma cells in a CAPNS1-dependent manner. As reported for other autophagy triggers, thapsigargin treatment induces Golgi fragmentation and fusion of Atg9/Bif-1-containing vesicles with LC3 bodies in control cells. By contrast, CAPNS1 depletion is coupled with an accumulation of LC3 bodies and Rab5 early endosomes. Moreover, Atg9 and Bif-1 remain in the GM130-positive Golgi stacks and Atg9 fails to interact with the endocytic route marker transferrin receptor and with the core autophagic protein Vps34 in CAPNS1-depleted cells. Ectopic expression of a Bif-1 point mutant resistant to calpain processing is coupled to endogenous p62 and LC3-II accumulation. Altogether, these data indicate that calpain allows dynamic flux of Atg9/Bif-1 vesicles from the Golgi toward the budding autophagosome.

Item Type:	Article
Uncontrolled Keywords:	Calpain, CAPNS1, Bif-1, Endophilin B1, Autophagy, Thapsigargin
Depositing User:	Symplectic Admin
Date Deposited:	08 Jun 2017 15:47
Last Modified:	19 Jan 2023 07:03
DOI:	10.1242/bio.022806
Open Access URL:	http://bio.biologists.org/content/6/5/551.long
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3007884