KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a

Lin Song, Shi Tang, Xiaolei Han, Ziying Jiang, Lingling Dong, Cuicui Liu, Xiaoyan Liang, Jixin Dong, Chengxuan Qiu, Yongxiang Wang, Yifeng Du

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Exosomes are nanosized membrane vesicles released from cells after fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) and play important roles in intercellular communication and numerous biological processes. However, the molecular mechanisms regulating exosome secretion remain poorly understood. Here we identify KIBRA as an adaptor-like protein that stabilizes Rab27a, which in turn controls exosome secretion both in vitro and in vivo. Knockdown or overexpression of KIBRA in neuronal and podocyte cell lines leads to a decrease or increase of exosome secretion, respectively, and KIBRA depletion increases MVB size and number. Comparing protein profiles between KIBRA knockout and wild-type mouse brain showed significantly decreased Rab27a, a small GTPase that regulates MVB-PM docking. Rab27a is stabilized by interacting with KIBRA, which prevents ubiquitination and degradation via the ubiquitin-proteasome pathway. In conclusion, we show that KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a.

Original languageEnglish (US)
Article number1639
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Song, L., Tang, S., Han, X., Jiang, Z., Dong, L., Liu, C., Liang, X., Dong, J., Qiu, C., Wang, Y., & Du, Y. (2019). KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a. Nature communications, 10(1), [1639]. https://doi.org/10.1038/s41467-019-09720-x