Rab23 regulates Nodal signaling in vertebrate left–right patterning independently of the Hedgehog pathway

Fuller, Kimberly; O’Connell, Joyce T.; Jack, Gordon; Mauti, Olivier; Eggenschwiler, Jonathan

doi:10.1016/j.ydbio.2014.04.012

Cited by 33 publications

(41 citation statements)

References 82 publications

(89 reference statements)

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“…However, an in vivo study has demonstrated that Rab8 is dispensable for ciliogenesis, as cilia are formed normally in Rab8a and Rab8b double mutant mice (Sato et al, 2014). Similarly, cell culture studies have suggested that Rab23 is involved in ciliogenesis (Lim and Tang, 2015;Yoshimura et al, 2007), but the in vivo evidence does not support that (Eggenschwiler et al, 2001;Fuller et al, 2014). Thus, to our knowledge, no Rab proteins have been so far linked to ciliogenesis in vivo and Rab34 is the first one shown to be required for ciliogenesis in vivo.…”

Section: Discussionmentioning

confidence: 95%

“…Rab23 also maintains ciliary steady state of Smo (Boehlke et al, 2010). Nevertheless, cilia form normally in Rab23 mutant mice (Fuller et al, 2014) and, so far, no Rab proteins have been linked to ciliogenesis in vivo. In addition, no Rab GTPases have been shown to regulate the fusion of preciliary vesicles to generate ciliary vesicleseven in cultured cells.…”

Section: Introductionmentioning

confidence: 99%

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Rab34 small GTPase is required for Hedgehog signaling and an early step of ciliary vesicle formation in mouse

Liu

Meng

et al. 2018

Journal of Cell Science

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The primary cilium is a microtubule-based organelle that protrudes from the cell surface and plays essential roles in embryonic development. Ciliogenesis begins with the successive fusion of preciliary vesicles to form ciliary vesicles, which then dock onto the distal end of the mother centriole. Rab proteins have been linked to cilia formation in cultured cells, but not yet in vivo. In the present study, we demonstrate that endocytic recycling protein Rab34 localizes to cilia, and that its mutation results in significant decrease of ciliogenesis in both cultured cells and mice. Rab34 is required for the successive fusion of preciliary vesicles to generate ciliary vesicles and for the migration of the mother centriole from perinuclear region to plasma membrane. We also show that Rab34 mutant mice exhibit polydactyly, and cleft-lip and-palate. These phenotypes are consistent with observations that nonciliated Rab34 mutant cells fail to respond to Hedgehog signaling and that processing of full-length Gli3 to its C-terminally truncated form is reduced in Rab34 mutant embryos. Therefore, Rab34 is required for an early step of ciliary vesicle formation and Hh signaling in vivo. This article has an associated First Person interview with the first author of the paper.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Rab34 small GTPase is required for Hedgehog signaling and an early step of ciliary vesicle formation in mouse

Liu

Meng

et al. 2018

Journal of Cell Science

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“…Chi et al (21) reported that Rab23 could negatively regulate Gli1 in a SUFU-dependent manner. However, Fuller et al (22) reported that Rab23 promotes nodal signaling in vertebrate left-right patterning independent of the Shh signaling pathway. In the present study, it was demonstrated that Rab23 upregulated ABCG2 expression via the Shh-Gli signal pathway in OC cells.…”

Section: Discussionmentioning

confidence: 99%

Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway

Zhang

Feng²,

Wang

et al. 2018

Oncol Lett

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Abstract.As a novel member of the Rab GTPase family, the role of Rab23 has been reported in multiple types of tumor. However, to the best of our knowledge, the role of Rab23 in ovarian cancer (OC) has not yet been reported. In the present study, immunohistochemistry analysis demonstrated that Rab23 was upregulated in OC tissue; survival analysis indicated that Rab23 expression was associated with a reduced overall survival (OS) rate and disease-free survival (DFS) time. In vitro experiments also demonstrated the increased expression of Rab23 in the OC cells lines, A2780 and SKOV-3, compared with in the normal ovarian cell line, IOSE80. Following the silencing of ABCG2 in SKOV-3 cells, ATP-binding cassette sub-family G member 2 (ABCG2) expression was significantly downregulated both at the RNA and protein levels. The cisplatin (DDP) IC 50 declined from 43.09±7.12 µmol/l in control cells to 26.46±5.38 µmol/l in SKOV-3 cells with silenced Rab23. In contrast, in A2780 cells overexpressing Rab23 (A2780-Rab23), ABCG2 expression was significantly upregulated and the DDP IC 50 increased from 27.42±6.54 µmol/l in control cells to 45.92±5.23 µmol/l in A2780-Rab23. Investigation into the potential molecular mechanisms for this revealed that the expression of sonic hedgehog (Shh) and Gli family zinc finger 1 (Gli1) was increased in A2780-Rab23 cells, whereas silencing Rab23 in SKOV-3 cells significantly inhibited the expression of Shh and Gli1. The Gli1 inhibitor GANT-61 significantly abrogated the increased ABCG2 expression in A2780-Rab23 cells. Furthermore, the DDP IC 50 in A2780-Rab23 cells decreased significantly following the silencing of ABCG2 expression; the IC 50 declined from 51.66±8.32 µmol/l in A2780-Rab23 cells to 25.61±6.17 µmol/l in A2780-Rab23 cells with silenced ABCG2. Collectively, the results indicate that Rab23 promotes the DDP resistance of OC cells via the Shh-Gli1-ABCG2 pathway, providing the proof of principle for the further investigation of drug resistance therapy targeting Rab23.

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“…The present study posed and verified the hypothesis that the hedgehog signaling pathway activates the PI3K/AKT pathway, which subsequently upregulates the expression of MMP-2 and MMP-9 at the mRNA and protein level, thereby mediating GBM migration and invasion. The hedgehog signaling pathway has a vital role in the control of cell differentiation, cell proliferation and embryonic development (5,7,12). According to recent studies, aberrant activation of hedgehog signaling is linked to the aggressiveness of multiple tumor types, including GBM (21,22).…”

Section: Discussionmentioning

confidence: 99%

“…The hedgehog signaling pathway is essential for embryonic patterning and cancer development (5)(6)(7). The hedgehog protein family includes desert hedgehog, Indian hedgehog and sonic hedgehog (SHH).…”

Section: Introductionmentioning

confidence: 99%

Activation of sonic hedgehog signaling enhances cell migration and invasion by induction of matrix metalloproteinase-2 and -9 via the phosphoinositide-3 kinase/AKT signaling pathway in glioblastoma

Chang

Zhao

Liu

et al. 2015

Molecular Medicine Reports

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Abstract. Aberrant hedgehog signaling contributes to the development of various malignancies, including glioblastoma (GBM). However, the potential mechanism of hedgehog signaling in GBM migration and invasion has remained to be elucidated. The present study showed that enhanced hedgehog signaling by recombinant human sonic hedgehog N-terminal peptide (rhSHH) promoted the adhesion, invasion and migration of GBM cells, accompanied by increases in mRNA and protein levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. However, inhibition of hedgehog signaling with cyclopamine suppressed the adhesion, invasion and migration of GBM cells, accompanied by decreases in mRNA and protein levels of MMP-2 and -9. Furthermore, it was found that MMP-2-and MMP-9-neutralizing antibodies or GAM6001 reversed the inductive effects of rhSHH on cell migration and invasion. In addition, enhanced hedgehog signaling by rhSHH increased AKT phosphorylation, whereas blockade of hedgehog signaling decreased AKT phosphorylations. Further experiments showed that LY294002, an inhibitor of phosphoinositide-3 kinase (PI3K), decreased rhSHH-induced upregulation of MMP-2 and -9. Finally, the protein expression of glioblastoma-associated oncogene 1 was positively correlated with levels of phosphorylated AKT as well as protein expressions of MMP-2 and -9 in GBM tissue samples. In conclusion, the present study indicated that the hedgehog pathway regulates GBM-cell migration and invasion by increasing MMP-2 and MMP-9 production via the PI3K/AKT pathway.

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Rab23 regulates Nodal signaling in vertebrate left–right patterning independently of the Hedgehog pathway

Cited by 33 publications

References 82 publications

Rab34 small GTPase is required for Hedgehog signaling and an early step of ciliary vesicle formation in mouse

Rab34 small GTPase is required for Hedgehog signaling and an early step of ciliary vesicle formation in mouse

Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway

Activation of sonic hedgehog signaling enhances cell migration and invasion by induction of matrix metalloproteinase-2 and -9 via the phosphoinositide-3 kinase/AKT signaling pathway in glioblastoma

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