Yes-associated protein homolog, YAP-1, is involved in the thermotolerance and aging in the nematode Caenorhabditis elegans

Iwasa, Hiroaki; Maimaiti, Sainawaer; Kuroyanagi, Hidehito; Kawano, Shodai; Inami, Kazutoshi; Timalsina, Shikshya; Ikeda, Mitsunobu; Nakagawa, Kentaro; Hata, Yoshinobu

doi:10.1016/j.yexcr.2013.01.020

Cited by 44 publications

(57 citation statements)

References 57 publications

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“…Specifically, we made transcriptional ‘promoter fusion’ reporters (endogenous gene promoter fused to GFP) for CCDC-104, CCDC-149 and RAB-28, and translational ‘protein fusion’ reporters (endogenous gene promoter + genomic exon/intron or cDNA sequence fused to GFP) for all 7 candidates. The only exception was the YAP-1 translational reporter, where the bbs-8 gene promoter active only in ciliated cells [57] was used because of the widespread expression of YAP-1 in multiple tissues and cell types [58]. We also made a second RAB-28 translational reporter driven by the bbs-8 gene promoter.…”

Section: Resultsmentioning

confidence: 99%

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport

et al. 2016

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Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa and Bardet-Biedl syndrome (BBS), frequently affecting many physiological and developmental processes across multiple organs. Cilium formation, maintenance and function depend on intracellular transport systems such as intraflagellar transport (IFT), which is driven by kinesin-2 and IFT-dynein motors and regulated by the Bardet-Biedl syndrome (BBS) cargo-adaptor protein complex, or BBSome. To identify new cilium-associated genes, we employed the nematode C. elegans, where ciliogenesis occurs within a short timespan during late embryogenesis when most sensory neurons differentiate. Using whole-organism RNA-Seq libraries, we discovered a signature expression profile highly enriched for transcripts of known ciliary proteins, including FAM-161 (FAM161A orthologue), CCDC-104 (CCDC104), and RPI-1 (RP1/RP1L1), which we confirm are cilium-localised in worms. From a list of 185 candidate ciliary genes, we uncover orthologues of human MAP9, YAP, CCDC149, and RAB28 as conserved cilium-associated components. Further analyses of C. elegans RAB-28, recently associated with autosomal-recessive cone-rod dystrophy, reveal that this small GTPase is exclusively expressed in ciliated neurons where it dynamically associates with IFT trains. Whereas inactive GDP-bound RAB-28 displays no IFT movement and diffuse localisation, GTP-bound (activated) RAB-28 concentrates at the periciliary membrane in a BBSome-dependent manner and undergoes bidirectional IFT. Functional analyses reveal that whilst cilium structure, sensory function and IFT are seemingly normal in a rab-28 null allele, overexpression of predicted GDP or GTP locked variants of RAB-28 perturbs cilium and sensory pore morphogenesis and function. Collectively, our findings present a new approach for identifying ciliary proteins, and unveil RAB28, a GTPase most closely related to the BBS protein RABL4/IFT27, as an IFT-associated cargo with BBSome-dependent cell autonomous and non-autonomous functions at the ciliary base.

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Section: Resultsmentioning

confidence: 99%

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport

et al. 2016

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“…Little is known about whether YAP/TAZ play a role in other phenotypes of aging. Deficiency in c.elegans yap-1 resulted in overall healthier aging relative to controls(Iwasa et al, 2013). Disrupted Hippo signaling in human and mouse ovarian follicles, which caused YAP activation, promoted growth and oocyte maturation, which are processes typically defective with age(Kawamura et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Age-Related Dysfunction in Mechanotransduction Impairs Differentiation of Human Mammary Epithelial Progenitors

et al. 2014

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Summary Dysfunctional progenitor and luminal cells with acquired basal cell properties accumulate during human mammary epithelia aging for reasons not understood. Multipotent progenitors from women aged <30 years were exposed to a physiologically relevant range of matrix elastic modulus, and increased rigidity caused a differentiation bias towards myoepithelial cells while reducing production of luminal cells and progenitor maintenance. Lineage representation in progenitors from women >55 years was unaffected by physiological modulus changes. Efficient activation of Hippo pathway transducers YAP and TAZ was required for the modulus-dependent myoepithelial/basal-bias in younger progenitors. In older progenitors YAP/TAZ were only activated when stressed by extra-physiologically rigid matrices, which biased differentiation towards luminal-like phenotypes. YAP was primarily active in myoepithelia of younger breast tissues, but activity increased in luminal cells with age. Thus aging phenotypes of mammary epithelia may arise partly because alterations in Hippo pathway activation affect the processes of progenitor differentiation and lineage specificity.

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“…Recent work in C. elegans has also identified a YAP homolog, which was named YAP-1 (Iwasa et al, 2013). The gene duplication leading to TAZ and YAP occurred in vertebrates, and their dynamic expression patterns play essential roles in the development of various organs in Xenopus tropicalis and Danio rerio (Hong et al, 2005;Hu et al, 2013;Jiang et al, 2009;Nejigane et al, 2011).…”

Section: Box 1 Evolutionary Conservation Of the Hippo Pathwaymentioning

confidence: 99%

The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease

2014

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Studies over the past 20 years have defined the Hippo signaling pathway as a major regulator of tissue growth and organ size. Diverse roles for the Hippo pathway have emerged, the majority of which in vertebrates are determined by the transcriptional regulators TAZ and YAP (TAZ/YAP). Key processes regulated by TAZ/YAP include the control of cell proliferation, apoptosis, movement and fate. Accurate control of the levels and localization of these factors is thus essential for early developmental events, as well as for tissue homeostasis, repair and regeneration. Recent studies have revealed that TAZ/YAP activity is regulated by mechanical and cytoskeletal cues as well as by various extracellular factors. Here, I provide an overview of these and other regulatory mechanisms and outline important developmental processes controlled by TAZ and YAP.

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Yes-associated protein homolog, YAP-1, is involved in the thermotolerance and aging in the nematode Caenorhabditis elegans

Cited by 44 publications

References 57 publications

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport

Age-Related Dysfunction in Mechanotransduction Impairs Differentiation of Human Mammary Epithelial Progenitors

The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease

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