@article{9dd27541343c41dd86af80bf9056e813,
title = "RAB11A and RAB11B control mitotic spindle function in intestinal epithelial progenitor cells",
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.",
keywords = "KIF11, RAB11A, RAB11B, mitosis, spindle",
author = "Ivor Joseph and Juan Flores and Victoria Farrell and Justin Davis and Jared Bianchi-Smak and Qiang Feng and Sayantani Goswami and Xiang Lin and Zhi Wei and Kevin Tong and Zhaohui Feng and Verzi, {Michael P.} and Bonder, {Edward M.} and Goldenring, {James R.} and Nan Gao",
note = "Funding Information: This work was supported by NIH grants R01DK102934, R01AT010243, R01DK132885, R01DK119198, R21AI167079, 3R01DK119198-03S1, and NSF/DBI 1952823 to N.G. NIH R15HG012087 to W.Z. NJDOH/NJ Commission on Cancer Research DCHS19PPC038 to J.F. and COCR24PRF017 to J.B.S., DK121915 and DK126446 to M.P.V., RC2 DK118640 and R01 DK48370 to J.R.G., R01CA214746 to Z.F. The authors acknowledge the support from the Advanced Imaging Core Facility of the Department of Biological Sciences and the instrumental grant funding from the NSF-MRI (2117484). The mass spectrometry data were obtained from an Orbitrap mass spectrometer funded in part by NIH grants 1S10OD025047-01, for the support of proteomics research at Rutgers Newark campus. Funding Information: This work was supported by NIH grants R01DK102934, R01AT010243, R01DK132885, R01DK119198, R21AI167079, 3R01DK119198‐03S1, and NSF/DBI 1952823 to N.G. NIH R15HG012087 to W.Z. NJDOH/NJ Commission on Cancer Research DCHS19PPC038 to J.F. and COCR24PRF017 to J.B.S., DK121915 and DK126446 to M.P.V., RC2 DK118640 and R01 DK48370 to J.R.G., R01CA214746 to Z.F. The authors acknowledge the support from the Advanced Imaging Core Facility of the Department of Biological Sciences and the instrumental grant funding from the NSF‐MRI (2117484). The mass spectrometry data were obtained from an Orbitrap mass spectrometer funded in part by NIH grants 1S10OD025047‐01, for the support of proteomics research at Rutgers Newark campus. Publisher Copyright: {\textcopyright} 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.",
year = "2023",
month = sep,
day = "6",
doi = "10.15252/embr.202256240",
language = "English (US)",
volume = "24",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "9",
}