RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins ARMC8α and ARMC8β are components of the CTLH complex

Kobayashi, Nobuaki; Yang, Jun; Ueda, Atsushi; Suzuki, Takaaki; Tomaru, Kouji; Takeno, Mitsuhiro; Okuda, Kenji; Ishigatsubo, Yoshiaki

doi:10.1016/j.gene.2007.02.032

Cited by 100 publications

(171 citation statements)

References 39 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…WDR47 plays a role in the regulation of microtubule dynamics, progenitor proliferation, neuronal migration, and fiber tract projections in a similar fashion to LIS1 (50,51) but with the distinctive particularity that WDR47 inhibits autophagic flux. This provides a functional link between autophagy biology and the CTLH domain (52) in mammals [this association was previously made with the vacuole import and degradation pathways in yeast (53)], while strengthening the emerging link between autophagy and microtubules assembly. Although a definite association of WDR47 with human brain disorders has not been made yet, WDR47 should be considered as a candidate gene for corpus callosum abnormalities and motor coordination deficiencies, possibly through compound heterozygosity or somatic mosaicism.…”

Section: Discussionmentioning

confidence: 60%

WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy

Kannan

Bayam

Wagner

et al. 2017

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

110

View full text Add to dashboard Cite

The family of WD40-repeat (WDR) proteins is one of the largest in eukaryotes, but little is known about their function in brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact in neuronal morphology when inactivated in mice. Remarkably, all seven genes showed corpus callosum defects, including thicker (Atg16l1, Coro1c, Dmxl2, and Herc1), thinner (Kif21b and Wdr89), or absent corpus callosum (Wdr47), revealing a common role for WDR genes in brain connectivity. We focused on the poorly studied WDR47 protein sharing structural homology with LIS1, which causes lissencephaly. In a dosage-dependent manner, mice lacking Wdr47 showed lethality, extensive fiber defects, microcephaly, thinner cortices, and sensory motor gating abnormalities. We showed that WDR47 shares functional characteristics with LIS1 and participates in key microtubule-mediated processes, including neural stem cell proliferation, radial migration, and growth cone dynamics. In absence of WDR47, the exhaustion of late cortical progenitors and the consequent decrease of neurogenesis together with the impaired survival of late-born neurons are likely yielding to the worsening of the microcephaly phenotype postnatally. Interestingly, the WDR47-specific C-terminal to LisH (CTLH) domain was associated with functions in autophagy described in mammals. Silencing WDR47 in hypothalamic GT1-7 neuronal cells and yeast models independently recapitulated these findings, showing conserved mechanisms. Finally, our data identified superior cervical ganglion-10 (SCG10) as an interacting partner of WDR47. Taken together, these results provide a starting point for studying the implications of WDR proteins in neuronal regulation of microtubules and autophagy.WD40-repeat proteins | corpus callosum agenesis | microcephaly | neurogenesis | autophagy T he function of WD40-repeat (WDR)-containing proteins, one of the largest eukaryotic protein families, is largely unknown. Their importance is, however, evident based on their highly conserved repeating units from bacteria to mammals (1), commonly made of seven repetitive blades of 40 amino acids that end with a tryptophan-aspartic acid dipeptide at the C terminus.As shown by crystallography studies, including the crystal structure of the beta gamma dimer of the G-protein transducin (2), a classical WDR protein, all WDR proteins are predicted to fold into a circularized beta-propeller structure, serving as a rigid platform (or scaffold) for protein-protein interactions by providing many stable and symmetrical surfaces (3, 4). One reason why WDR domains may have been less studied than other common domains, such as kinases or PDZ or SH3 domains (3), is that no WDR domain has yet been found with catalytic activity (3), but this does not mean that the scaffold domains are less important. To the contrary, their serving as a platform for multiple enzymatic reactions and signaling events is highly significant (5).In recent years, human genetic studies have also begun to recognize the importance of WDR gen...

show abstract

Section: Discussionmentioning

confidence: 60%

WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy

Kannan

Bayam

Wagner

et al. 2017

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

110

View full text Add to dashboard Cite

show abstract

“…that will help to elucidate its as yet only vaguely described function (26). Further effort will be needed to determine the function of this complex, possibly in the context of dyneindriven IFT as suggested by EPASIS.…”

Section: Discussionmentioning

confidence: 99%

Elution Profile Analysis of SDS-induced Subcomplexes by Quantitative Mass Spectrometry

Texier

Toedt

Gorza

et al. 2014

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Analyzing the molecular architecture of native multiprotein complexes via biochemical methods has so far been difficult and error prone. Protein complex isolation by affinity purification can define the protein repertoire of a given complex, yet, it remains difficult to gain knowledge of its substructure or modular composition. Here, we introduce SDS concentration gradient induced decomposition of protein complexes coupled to quantitative mass spectrometry and in silico elution profile distance analysis. By applying this new method to a cellular transport module, the IFT/lebercilin complex, we demonstrate its ability to determine modular composition as well as sensitively detect known and novel complex components. We show that the IFT/lebercilin complex can be separated into at least five submodules, the IFT complex A, the IFT complex B, the 14 -3-3 protein complex and the CTLH complex, as well as the dynein light chain complex. Understanding the orchestration and dynamics of cellular function on the molecular level is one of the challenges in biology. It is now clear that cell regulatory decisions are made by molecular switching events in large but highly dynamic, often coalescing, protein complexes (1, 2). Protein complex isolation by affinity purification is a common technique, used for the identification of the protein composition of these molecular machines (3), contributing to the elucidation of spatial and temporal patterns of large protein networks and functional modules within these networks (4). Interaction data derived from different protein complex analyses are the basis for predictions of biological pathways or disease mechanisms concerning those proteins (5). Still, in most cases it is difficult or even impossible to determine how, or even if the copurified proteins assemble as a single module in a cell, limiting the fine-grained description of the complex structure (6, 7). The possibility to integrate module and submodule information in higher order protein networks is extremely valuable for their understanding and opens the route to define pathways of information flow within and between discrete molecular machines. Zooming in on a protein mutated in early childhood blindness, lebercilin, we have previously identified proteins of the intraflagellar transport (IFT) machinery to interact with lebercilin (5). IFT appears as a physical entity driving vesicular trafficking through the connecting cilium that bridges the inner and the outer segment of vertebrate photoreceptors (8). IFT, like many other multiprotein complexes, is an example for a functionally fairly well described molecular machine with yet unknown molecular topology and mechanical properties.To determine composition, as well as protein complex topology of lebercilin and its interaction with IFT components, we developed a novel workflow, which we termed "elution profile analysis of SDS-induced subcomplexes by quantitative From the ‡Division

show abstract

“…RMND5A is a key component of the CTLH complex (C-terminal to lissencephaly type-1-like homology motif). This complex is involved in microtubule dynamics, cell migration, nucleokinesis and chromosome segregation (28). Therefore, the variations in the expression of the RMND5A gene may be due to the effects of paclitaxel.…”

Section: Discussionmentioning

confidence: 99%

Changes in leukocyte gene expression profiles induced by antineoplastic chemotherapy

et al. 2012

View full text Add to dashboard Cite

Abstract. In the present study, we studied changes in gene expression induced by chemotherapy (CT) on normal peripheral blood leukocytes (PBLs), at baseline and following three CT cycles, in order to identify which genes were specifically affected and were potentially useful as biomarkers for a personalised prognosis and follow-up. A PBL subtraction cDNA library was constructed from four patients undergoing CT with paclitaxel and carboplatin

show abstract

RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins ARMC8α and ARMC8β are components of the CTLH complex

Cited by 100 publications

References 39 publications

WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy

WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy

Elution Profile Analysis of SDS-induced Subcomplexes by Quantitative Mass Spectrometry

Changes in leukocyte gene expression profiles induced by antineoplastic chemotherapy

Contact Info

Product

Resources

About