Rabs and the exocyst in ciliogenesis, tubulogenesis and beyond

Das, Amlan; Guo, Wei

doi:10.1016/j.tcb.2011.03.006

Cited by 102 publications

(100 citation statements)

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“…Interestingly, the Rab family GTPase Rab11, which regulates recycling endosomes and vesicle trafficking from the trans-Golgi (Das and Guo, 2011), controls cilia length (Knödler et al, 2010) and the sorting and basolateral transport of E-cadherin in mammalian cell cultures (Lock and Stow, 2005). In zebrafish, MO knockdown of Rab11a has been recently shown to reduce KV lumen size (Westlake et al, 2011), similar to the KV phenotype observed in Lgl2 MO embryos.…”

Section: Lgl2 Genetically Interacts With Rab11a To Regulate E-cadherimentioning

confidence: 80%

Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle

et al. 2013

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SUMMARYMotile cilia perform crucial functions during embryonic development and throughout adult life. Development of organs containing motile cilia involves regulation of cilia formation (ciliogenesis) and formation of a luminal space (lumenogenesis) in which cilia generate fluid flows. Control of ciliogenesis and lumenogenesis is not yet fully understood, and it remains unclear whether these processes are coupled. In the zebrafish embryo, lethal giant larvae 2 (lgl2) is expressed prominently in ciliated organs. Lgl proteins are involved in establishing cell polarity and have been implicated in vesicle trafficking. Here, we identified a role for Lgl2 in development of ciliated epithelia in Kupffer's vesicle, which directs left-right asymmetry of the embryo; the otic vesicles, which give rise to the inner ear; and the pronephric ducts of the kidney. Using Kupffer's vesicle as a model ciliated organ, we found that depletion of Lgl2 disrupted lumen formation and reduced cilia number and length. Immunofluorescence and time-lapse imaging of Kupffer's vesicle morphogenesis in Lgl2-deficient embryos suggested cell adhesion defects and revealed loss of the adherens junction component E-cadherin at lateral membranes. Genetic interaction experiments indicate that Lgl2 interacts with Rab11a to regulate E-cadherin and mediate lumen formation that is uncoupled from cilia formation. These results uncover new roles and interactions for Lgl2 that are crucial for both lumenogenesis and ciliogenesis and indicate that these processes are genetically separable in zebrafish.

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Section: Lgl2 Genetically Interacts With Rab11a To Regulate E-cadherimentioning

confidence: 80%

Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle

et al. 2013

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“…Exocyst subunits have been detected at the base or inside of primary cilia by immunofluorescence microscopy or EM; inhibition of exocyst function affected ciliogenesis (Rogers et al, 2004;Zuo et al, 2009;Feng et al, 2012). In addition, an interaction network between Rab11, Rabin8 (the guanine nucleotide exchange factor for Rab8), Rab8 and the exocyst complex regulates primary ciliogenesisprobably by mediating the transport of transmembrane proteins or basal bodies to the cilia membrane, although further experimental evidence is needed to support this hypothesis Das and Guo, 2011;Feng et al, 2012). Rab10 also interacts with the exocyst and mediate ciliogenesis in renal epithelial cells, probably through a similar mechanism (Babbey et al, 2010).…”

Section: The Exocyst In Primary Ciliogenesismentioning

confidence: 99%

The Exocyst at a Glance

Guo

2015

Journal of Cell Science

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The exocyst is an octameric protein complex that is implicated in the tethering of secretory vesicles to the plasma membrane prior to SNARE-mediated fusion. Spatial and temporal control of exocytosis through the exocyst has a crucial role in a number of physiological processes, such as morphogenesis, cell cycle progression, primary ciliogenesis, cell migration and tumor invasion. In this Cell Science at a Glance poster article, we summarize recent works on the molecular organization, function and regulation of the exocyst complex, as they provide rationales to the involvement of this complex in such a diverse array of cellular processes.

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“…Although studies in yeast and mammalian cells have revealed different types of regulation of Sec2p/Rabin8 by Ypt32p/Rab11 (i.e., membrane recruitment vs. kinetic activation), the Rab cascade serves to coordinate the generation of vesicles from the donor compartments to its subsequent transport and fusion (3,4,19,20). The Rab11-Rabin8-Rab8 signaling cascade is implicated in a number of cell biological processes, such as primary ciliogenesis and cystogenesis (16,17,20,21).…”

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confidence: 99%

Activation of Rab8 guanine nucleotide exchange factor Rabin8 by ERK1/2 in response to EGF signaling

Wang

Ren

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Exocytosis is tightly regulated in many cellular processes, from neurite expansion to tumor proliferation. Rab8, a member of the Rab family of small GTPases, plays an important role in membrane trafficking from the trans-Golgi network and recycling endosomes to the plasma membrane. Rabin8 is a guanine nucleotide exchange factor (GEF) and major activator of Rab8. Investigating how Rabin8 is activated in cells is thus pivotal to the understanding of the regulation of exocytosis. Here we show that phosphorylation serves as an important mechanism for Rabin8 activation. We identified Rabin8 as a direct phospho-substrate of ERK1/2 in response to EGF signaling. At the molecular level, ERK phosphorylation relieves the autoinhibition of Rabin8, thus promoting its GEF activity. We further demonstrate that blocking ERK1/2-mediated phosphorylation of Rabin8 inhibits transferrin recycling to the plasma membrane. Together, our results suggest that ERK1/2 activate Rabin8 to regulate vesicular trafficking to the plasma membrane in response to extracellular signaling.Rab GTPases | Rab8 | guanine nucleotide exchange factor | ERK | phosphorylation

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Rabs and the exocyst in ciliogenesis, tubulogenesis and beyond

Cited by 102 publications

References 50 publications

Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle

Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle

The Exocyst at a Glance

Activation of Rab8 guanine nucleotide exchange factor Rabin8 by ERK1/2 in response to EGF signaling

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