title: Rab11a is required for apical protein localisation in the intestine.
abstract: The small GTPase Rab11 plays an important role in the recycling of proteins to the plasma membrane as well as in polarised transport in epithelial cells and neurons. We generated conditional knockout mice deficient in Rab11a. Rab11a-deficient mice are embryonic lethal, and brain-specific Rab11a knockout mice show no overt abnormalities in brain architecture. In contrast, intestine-specific Rab11a knockout mice begin dying approximately 1 week after birth. Apical proteins in the intestines of knockout mice accumulate in the cytoplasm and mislocalise to the basolateral plasma membrane, whereas the localisation of basolateral proteins is unaffected. Shorter microvilli and microvillus inclusion bodies are also observed in the knockout mice. Elevation of a serum starvation marker was also observed, likely caused by the mislocalisation of apical proteins and reduced nutrient uptake. In addition, Rab8a is mislocalised in Rab11a knockout mice. Conversely, Rab11a is mislocalised in Rab8a knockout mice and in a microvillus atrophy patient, which has a mutation in the myosin Vb gene. Our data show an essential role for Rab11a in the localisation of apical proteins in the intestine and demonstrate functional relationships between Rab11a, Rab8a and myosin Vb in vivo.
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Sobajima
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Yoshimura
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Iwano
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kunii
authors.affiliation: Department of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Nur
authors.initials: N
authors.lastname: Atik
authors.affiliation: Department of Pediatrics, Nara Hospital, Kinki University School of Medicine, Ikoma, Nara, 630-0293, Japan.
authors.forename: Sotaro
authors.initials: S
authors.lastname: Mushiake
authors.affiliation: Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koyama
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan aharada@acb.med.osaka-u.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Harada
keywords: Apical membrane; Brain; Cell polarity; Intestine; Knockout mouse; Rab11a