RAB11A and RAB11B control mitotic spindle function in intestinal epithelial progenitor cells

Ivor Joseph, Juan Flores, Victoria Farrell, Justin Davis, Jared Bianchi-Smak, Qiang Feng, Sayantani Goswami, Xiang Lin, Zhi Wei, Kevin Tong, Zhaohui Feng, Michael P. Verzi, Edward M. Bonder, James R. Goldenring, Nan Gao

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

RAB11 small GTPases and associated recycling endosome have been localized to mitotic spindles and implicated in regulating mitosis. However, the physiological significance of such regulation has not been observed in mammalian tissues. We have used newly engineered mouse models to investigate intestinal epithelial renewal in the absence of single or double isoforms of RAB11 family members: Rab11a and Rab11b. Comparing with single knockouts, mice with compound ablation demonstrate a defective cell cycle entry and robust mitotic arrest followed by apoptosis, leading to a total penetrance of lethality within 3 days of gene ablation. Upon Rab11 deletion ex vivo, enteroids show abnormal mitotic spindle formation and cell death. Untargeted proteomic profiling of Rab11a and Rab11b immunoprecipitates has uncovered a shared interactome containing mitotic spindle microtubule regulators. Disrupting Rab11 alters kinesin motor KIF11 function and impairs bipolar spindle formation and cell division. These data demonstrate that RAB11A and RAB11B redundantly control mitotic spindle function and intestinal progenitor cell division, a mechanism that may be utilized to govern the homeostasis and renewal of other mammalian tissues.

Original languageEnglish (US)
Article numbere56240
JournalEMBO Reports
Volume24
Issue number9
DOIs
StatePublished - Sep 6 2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

Keywords

  • KIF11
  • RAB11A
  • RAB11B
  • mitosis
  • spindle

Fingerprint

Dive into the research topics of 'RAB11A and RAB11B control mitotic spindle function in intestinal epithelial progenitor cells'. Together they form a unique fingerprint.

Cite this