RRC ID 4187
Author Sato T, Mushiake S, Kato Y, Sato K, Sato M, Takeda N, Ozono K, Miki K, Kubo Y, Tsuji A, Harada R, Harada A.
Title The Rab8 GTPase regulates apical protein localization in intestinal cells.
Journal Nature
Abstract A number of proteins are known to be involved in apical/basolateral transport of proteins in polarized epithelial cells. The small GTP-binding protein Rab8 was thought to regulate basolateral transport in polarized kidney epithelial cells through the AP1B-complex-mediated pathway. However, the role of Rab8 (Rab8A) in cell polarity in vivo remains unknown. Here we show that Rab8 is responsible for the localization of apical proteins in intestinal epithelial cells. We found that apical peptidases and transporters localized to lysosomes in the small intestine of Rab8-deficient mice. Their mislocalization and degradation in lysosomes led to a marked reduction in the absorption rate of nutrients in the small intestine, and ultimately to death. Ultrastructurally, a shortening of apical microvilli, an increased number of enlarged lysosomes, and microvillus inclusions in the enterocytes were also observed. One microvillus inclusion disease patient who shows an identical phenotype to Rab8-deficient mice expresses a reduced amount of RAB8 (RAB8A; NM_005370). Our results demonstrate that Rab8 is necessary for the proper localization of apical proteins and the absorption and digestion of various nutrients in the small intestine.
Volume 448(7151)
Pages 366-9
Published 2007-7-19
DOI 10.1038/nature05929
PII nature05929
PMID 17597763
MeSH Animals Cell Polarity* Cytoplasm / metabolism Epithelial Cells / cytology Epithelial Cells / enzymology Epithelial Cells / metabolism Epithelial Cells / pathology Humans Intestinal Absorption Intestinal Mucosa / metabolism* Intestines / cytology* Intestines / enzymology Intestines / pathology Lysosomes / metabolism Mice Mice, Knockout Microvilli / enzymology Microvilli / metabolism Microvilli / pathology Peptide Hydrolases / metabolism Protein Transport rab GTP-Binding Proteins / deficiency rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism*
IF 41.577
Times Cited 175
C.elegans tm2526