Identification of chaperonin CCTγ subunit as a determinant of retinotectal development by whole-genome subtraction cloning from zebrafish<i>no tectal neuron</i>mutant

Matsuda, Naoto; Mishina, Masayoshi

doi:10.1242/dev.01085

Cited by 30 publications

(27 citation statements)

References 84 publications

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“…(Scale bar, 100 μm.) also shared by cct genetic mutants (43,44). Together these results indicate that at least a subset of cct proteins interact with the BBS pathway in vivo.…”

Section: Requirement Of Chaperonin-like Bbs Proteins For Bbsome Assemmentioning

confidence: 61%

BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly

Seo

Baye²,

Schulz

et al. 2010

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

273

282

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Bardet-Biedl syndrome (BBS) is a human genetic disorder resulting in obesity, retinal degeneration, polydactyly, and nephropathy. Recent studies indicate that trafficking defects to the ciliary membrane are involved in this syndrome. Here, we show that a novel complex composed of three chaperonin-like BBS proteins (BBS6, BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBSome assembly, which transports vesicles to the cilia. Chaperoninlike BBS proteins interact with a subset of BBSome subunits and promote their association with CCT chaperonins. CCT activity is essential for BBSome assembly, and knockdown of CCT chaperonins in zebrafish results in BBS phenotypes. Many disease-causing mutations found in BBS6, BBS10, and BBS12 disrupt interactions among these BBS proteins. Our data demonstrate that BBS6, BBS10, and BBS12 are necessary for BBSome assembly, and that impaired BBSome assembly contributes to the etiology of BBS phenotypes associated with the loss of function of these three BBS genes.Bardet-Biedl Syndrome | ciliopathy | molecular chaperone | protein trafficking T he primary cilium is a microtubule-based subcellular organelle that projects from the surface of the cell. It plays an essential role in the transduction of extracellular signals (1, 2). In vertebrates, loss of cilia or ciliary dysfunction leads to various defects such as situs inversus, polydactyly, neural tube defects, and obesity (2-4). Ciliary dysfunction is also involved in several human genetic syndromes (2, 3). Bardet-Biedl syndrome (BBS) is one of the most studied human genetic disorders associated with ciliary dysfunction. Individuals with BBS display retinal degeneration, obesity, polydactyly, hypertension, hypogonadism, renal anomalies, and cognitive impairment (5-7). BBS displays autosomal recessive inheritance with extensive genetic heterogeneity.BBS proteins are required for the maintenance of ciliary structure and function. Mutation of BBS genes in mice results in absence of flagella in spermatozoa (8-10) and abnormalities in cilia in brain ependymal cells, airway epithelial cells (11,12) and olfactory neurons (13). At the molecular level, BBS proteins are involved in protein/vesicle trafficking along microtubules. For example, knockdown of BBS genes in zebrafish results in delay in retrograde melanosome transport, which is mediated by dynein motor proteins along the microtubule (14, 15). In C. elegans, mutations in bbs1, bbs7, or bbs8 cause defects in the movement of the intraflagellar transport (IFT) subcomplexes inside the cilium (16). During the last decade, twelve BBS genes (BBS1-12) have been identified (17-26). More recently, hypomorphic mutations in two additional genes (MKS1 and CEP290) were reported to be associated with BBS, representing BBS13 and BBS14, respectively (27). Null mutations in MKS1 and CEP290 cause Meckel-Gruber syndrome, a related but more severe disorder (28-30). Seven of the known BBS proteins (BBS1-2, BBS4-5, BBS7-9) have been shown to form a stable complex, the BBSome, and this complex is pr...

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“…(Scale bar, 100 μm.) also shared by cct genetic mutants (43,44). Together these results indicate that at least a subset of cct proteins interact with the BBS pathway in vivo.…”

Section: Requirement Of Chaperonin-like Bbs Proteins For Bbsome Assemmentioning

confidence: 61%

BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly

Seo

Baye²,

Schulz

et al. 2010

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

273

282

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“…until after 48 hpf, much later than that in dou yan mi234 (Matsuda and Mishina, 2004); and the dazed small eye mutant has normal retinal lamination (Perkins et al, 2005). These phenotypic differences suggest that the dou yan gene regulates the size of the eyes through a pathway different from the pathways that concern other identified genes.…”

Section: Discussionmentioning

confidence: 95%

“…Previous mutagenesis screens and reverse genetic approaches have identified several genes that are important in controlling the size of zebrafish eye: Rab11-FIP4, Mcm5, PITX3, small heart, no tectal neuron, and dazed (Matsuda and Mishina, 2004;Yuan and Joseph, 2004;Babb et al, 2005;Perkins et al, 2005;Shi et al, 2005;Ryu et al, 2005;Muto et al, 2006). These genes map to chromosome regions different from the one in which the dou yan gene resides.…”

Section: Discussionmentioning

confidence: 99%

Zebrafish dou yan mutation causes patterning defects and extensive cell death in the retina

Catalano

Raymond

Goldman

et al. 2007

Developmental Dynamics

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The size of an organ is largely determined by the number of cells it contains, which in turn is regulated by two opposing processes, cell proliferation and cell death, however, it is generally not clear how cell proliferation and cell death are coordinated during development. Here, we characterize the zebrafish dou yan mi234 mutation that results in a dramatic reduction of retinal size and a disruption of retinal differentiation and lamination. The retinal size reduction is caused by increased retinal cell death in a non-cell-autonomous manner during early development. The phenotypic defect in dou yan mi234 arises coincident with the onset of retinal neurogenesis and differentiation. Interestingly, unlike many other small eye mutations, the mutation does not increase the level of cell death in the brain, suggesting that the brain and retina use different mechanisms to maintain cell survival. Identification and further study of the dou yan gene will enhance our understanding of the molecular mechanisms regulating retinal cellular homeostasis, i.e., the balance between cell proliferation and cell death. Developmental Dynamics 236: 1295-1306, 2007.

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“…In this regard, it should be mentioned that a 143 base-pair deletion in the gene encoding the CCT gamma subunit of zebrafish has been implicated in developmental defects in this model organism. 35 …”

Section: Chaperonins Of Group II Mckusick-kaufman Syndromementioning

confidence: 99%

Genetic disorders involving molecular-chaperone genes: A perspective

Macario

Grippo

Macario

2005

Genetics in Medicine

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Molecular chaperones are important for maintaining a functional set of proteins in all cellular compartments.Together with protein degradation machineries (e.g., the ubiquitin-proteasome system), chaperones form the core of the cellular protein-quality control mechanism. Chaperones are proteins, and as such, they can be affected by mutations. At least 15 disorders have been identified that are associated with mutations in genes encoding chaperones, or molecules with features suggesting that they function as chaperones. These chaperonopathies and a few other candidates are presented in this article. In most cases, the mechanisms by which the defective genes contribute to the observed phenotypes are still uncharacterized. However, the reported observations definitely

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Identification of chaperonin CCTγ subunit as a determinant of retinotectal development by whole-genome subtraction cloning from zebrafishno tectal neuronmutant

Cited by 30 publications

References 84 publications

BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly

BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly

Zebrafish dou yan mutation causes patterning defects and extensive cell death in the retina

Genetic disorders involving molecular-chaperone genes: A perspective

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