Rab11 is required for lysosome exocytosis through the interaction with Rab3a, Sec15 and GRAB

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Abstract

Lysosomes are dynamic organelles, capable of undergoing exocytosis. This process is crucial for several cellular functions, namely plasma membrane repair. Nevertheless, the molecular machinery involved in this process is poorly understood. Here, we identify Rab11a and Rab11b as regulators of calcium-induced lysosome exocytosis. Interestingly, Rab11-positive vesicles transiently interact with lysosomes at the cell periphery, indicating that this interaction is required for the last steps of lysosome exocytosis. Additionally, we found that the silencing of the exocyst subunit Sec15, a Rab11 effector, impairs lysosome exocytosis, suggesting that Sec15 acts together with Rab11 in the regulation of lysosome exocytosis. Furthermore, we show that Rab11 binds the guanine nucleotide exchange factor for Rab3a (GRAB) and also Rab3a, which we described previously as a regulator of the positioning and exocytosis of lysosomes. Thus, our study identifies new players required for lysosome exocytosis and suggest the existence of a Rab11-Rab3a cascade involved in this process.

Original languageEnglish
Article numberjcs246694
JournalJournal Of Cell Science
Volume134
Issue number11
Early online date18 May 2021
DOIs
Publication statusPublished - 8 Jun 2021

Keywords

  • Exocytosis
  • GRAB
  • RAB3IL1
  • Lysosome
  • Rab11
  • Rab3a
  • Sec15

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