scholarly journals A ciliopathy complex builds distal appendages to initiate ciliogenesis

2021 ◽  
Author(s):  
Dhivya Kumar ◽  
Addison Rains ◽  
Vicente Herranz-Pérez ◽  
Quanlong Lu ◽  
Xiaoyu Shi ◽  
...  
Keyword(s):  
Early Step ◽  
Evolutionarily Conserved ◽  
Associated Proteins ◽  
Appendage Formation ◽  
Distal Centriole

ABSTRACTCells inherit two centrioles, the older of which is uniquely capable of generating a cilium. We identified that three evolutionarily conserved proteins that underlie human ciliopathies, CEP90, MNR and OFD1, form a complex. This complex localized to both distal centrioles and centriolar satellites, proteinaceous granules surrounding centrioles. Cells and mice lacking CEP90 or MNR did not generate cilia, failed to assemble distal appendages, and did not transduce Hedgehog signals. Disrupting the satellite pools did not affect distal appendage assembly, indicating that it is the centriolar populations of MNR and CEP90 that are critical for ciliogenesis. CEP90 recruited the most proximal known distal appendage component, CEP83, to root distal appendages formation, an early step in ciliogenesis. In addition to distal appendage formation, MNR, but not CEP90, restricted centriolar length by recruiting OFD1. We conclude that a complex of disease- associated proteins, MNR, OFD1 and CEP90, acts at the distal centriole to support ciliogenesis by restraining centriole length and assembling distal appendages.

scholarly journals A ciliopathy complex builds distal appendages to initiate ciliogenesis

2021 ◽  
Vol 220 (9) ◽  
Author(s):  
Dhivya Kumar ◽  
Addison Rains ◽  
Vicente Herranz-Pérez ◽  
Quanlong Lu ◽  
Xiaoyu Shi ◽  
...  
Keyword(s):  
Early Step ◽  
Appendage Formation ◽  
Distal Centriole

Cells inherit two centrioles, the older of which is uniquely capable of generating a cilium. Using proteomics and superresolved imaging, we identify a module that we term DISCO (distal centriole complex). The DISCO components CEP90, MNR, and OFD1 underlie human ciliopathies. This complex localizes to both distal centrioles and centriolar satellites, proteinaceous granules surrounding centrioles. Cells and mice lacking CEP90 or MNR do not generate cilia, fail to assemble distal appendages, and do not transduce Hedgehog signals. Disrupting the satellite pools does not affect distal appendage assembly, indicating that it is the centriolar populations of MNR and CEP90 that are critical for ciliogenesis. CEP90 recruits the most proximal known distal appendage component, CEP83, to root distal appendage formation, an early step in ciliogenesis. In addition, MNR, but not CEP90, restricts centriolar length by recruiting OFD1. We conclude that DISCO acts at the distal centriole to support ciliogenesis by restraining centriole length and assembling distal appendages, defects in which cause human ciliopathies.

A highly evolutionarily conserved mitochondrial protein is structurally related to the protein encoded by the Escherichia coli groEL gene

1988 ◽  
Vol 8 (1) ◽  
pp. 371-380
Author(s):  
T W McMullin ◽  
R L Hallberg
Keyword(s):  
Escherichia Coli ◽  
Tetrahymena Thermophila ◽  
Mitochondrial Protein ◽  
Cross Reactivity ◽  
Macromolecular Complexes ◽  
E Coli ◽  
Groel Gene ◽  
Evolutionarily Conserved ◽  
Associated Proteins ◽  
Related Proteins

We recently reported that a Tetrahymena thermophila 58-kilodalton (kDa) mitochondrial protein (hsp58) was selectively synthesized during heat shock. In this study, we show that hsp58 displayed antigenic similarity with mitochondrially associated proteins from Saccharomyces cerevisiae (64 kDa), Xenopus laevis (60 kDa), Zea mays (62 kDa), and human cells (59 kDa). Furthermore, a 58-kDa protein from Escherichia coli also exhibited antigenic cross-reactivity to an antiserum directed against the T. thermophila mitochondrial protein. The proteins from S. cerevisiae and E. coli antigenically related to hsp58 were studied in detail and found to share several other characteristics with hsp58, including heat inducibility and the property of associating into distinct oligomeric complexes. The T. thermophila, S. cerevisiae, and E. coli macromolecular complexes containing these related proteins had similar sedimentation characteristics and virtually identical morphologies as seen with the electron microscope. The distinctive properties of the E. coli homolog to T. thermophila hsp58 indicate that it is most likely the product of the groEL gene.

scholarly journals Non-Proteasomal UbL-UbA Family of Proteins in Neurodegeneration

2019 ◽  
Vol 20 (8) ◽  
pp. 1893 ◽  
Author(s):  
Salinee Jantrapirom ◽  
Luca Lo Piccolo ◽  
Masamitsu Yamaguchi
Keyword(s):  
Neurodegenerative Diseases ◽  
Family Members ◽  
Proteasomal Activity ◽  
New Findings ◽  
Evolutionarily Conserved ◽  
Associated Proteins ◽  
Ubiquitin Receptors ◽  
Drosophila Models

Ubiquitin-like/ubiquitin-associated proteins (UbL-UbA) are a well-studied family of non-proteasomal ubiquitin receptors that are evolutionarily conserved across species. Members of this non-homogenous family facilitate and support proteasomal activity by promoting different effects on proteostasis but exhibit diverse extra-proteasomal activities. Dysfunctional UbL-UbA proteins render cells, particularly neurons, more susceptible to stressors or aging and may cause earlier neurodegeneration. In this review, we summarized the properties and functions of UbL-UbA family members identified to date, with an emphasis on new findings obtained using Drosophila models showing a direct or indirect role in some neurodegenerative diseases.

scholarly journals A highly evolutionarily conserved mitochondrial protein is structurally related to the protein encoded by the Escherichia coli groEL gene.

1988 ◽  
Vol 8 (1) ◽  
pp. 371-380 ◽  
Author(s):  
T W McMullin ◽  
R L Hallberg
Keyword(s):  
Escherichia Coli ◽  
Tetrahymena Thermophila ◽  
Mitochondrial Protein ◽  
Cross Reactivity ◽  
Macromolecular Complexes ◽  
E Coli ◽  
Groel Gene ◽  
Evolutionarily Conserved ◽  
Associated Proteins ◽  
Related Proteins

We recently reported that a Tetrahymena thermophila 58-kilodalton (kDa) mitochondrial protein (hsp58) was selectively synthesized during heat shock. In this study, we show that hsp58 displayed antigenic similarity with mitochondrially associated proteins from Saccharomyces cerevisiae (64 kDa), Xenopus laevis (60 kDa), Zea mays (62 kDa), and human cells (59 kDa). Furthermore, a 58-kDa protein from Escherichia coli also exhibited antigenic cross-reactivity to an antiserum directed against the T. thermophila mitochondrial protein. The proteins from S. cerevisiae and E. coli antigenically related to hsp58 were studied in detail and found to share several other characteristics with hsp58, including heat inducibility and the property of associating into distinct oligomeric complexes. The T. thermophila, S. cerevisiae, and E. coli macromolecular complexes containing these related proteins had similar sedimentation characteristics and virtually identical morphologies as seen with the electron microscope. The distinctive properties of the E. coli homolog to T. thermophila hsp58 indicate that it is most likely the product of the groEL gene.

scholarly journals Human UBN1 Is an Ortholog of Yeast Hpc2p and Has an Essential Role in the HIRA/ASF1a Chromatin-Remodeling Pathway in Senescent Cells

2008 ◽  
Vol 29 (3) ◽  
pp. 758-770 ◽  
Author(s):  
Gowrishankar Banumathy ◽  
Neeta Somaiah ◽  
Rugang Zhang ◽  
Yong Tang ◽  
Jason Hoffmann ◽  
...  
Keyword(s):  
Tumor Suppression ◽  
Histone Chaperones ◽  
Human Orthologs ◽  
Evolutionarily Conserved ◽  
Associated Proteins ◽  
Pathway Formation ◽  
Multiple Species ◽  
Suppression Process ◽  
Tissue Aging ◽  
A Site

ABSTRACT Cellular senescence is an irreversible proliferation arrest, tumor suppression process and likely contributor to tissue aging. Senescence is often characterized by domains of facultative heterochromatin, called senescence-associated heterochromatin foci (SAHF), which repress expression of proliferation-promoting genes. Given its likely contribution to tumor suppression and tissue aging, it is essential to identify all components of the SAHF assembly pathway. Formation of SAHF in human cells is driven by a complex of histone chaperones, namely, HIRA and ASF1a. In yeast, the complex orthologous to HIRA/ASF1a contains two additional proteins, Hpc2p and Hir3p. Using a sophisticated approach to search for remote orthologs conserved in multiple species through evolution, we identified the HIRA-associated proteins, UBN1 and UBN2, as candidate human orthologs of Hpc2p. We show that the Hpc2-related domain of UBN1, UBN2, and Hpc2p is an evolutionarily conserved HIRA/Hir-binding domain, which directly interacts with the N-terminal WD repeats of HIRA/Hir. UBN1 binds to proliferation-promoting genes that are repressed by SAHF and associates with histone methyltransferase activity that methylates lysine 9 of histone H3, a site that is methylated in SAHF. UBN1 is indispensable for formation of SAHF. We conclude that UBN1 is an ortholog of yeast Hpc2p and a novel regulator of senescence.

scholarly journals Structural modularity of the XIST ribonucleoprotein complex

2019 ◽  
Author(s):  
Zhipeng Lu ◽  
Jimmy K. Guo ◽  
Yuning Wei ◽  
Diana R. Dou ◽  
Brian Zarnegar ◽  
...  
Keyword(s):  
Protein Complex ◽  
Protein Complexes ◽  
Effector Proteins ◽  
General Strategy ◽  
Sequence Motifs ◽  
Modular Architecture ◽  
Chimeric Rnas ◽  
Xist Rna ◽  
Evolutionarily Conserved ◽  
Associated Proteins

SUMMARYLong noncoding RNAs are thought to regulate gene expression by organizing protein complexes through unclear mechanisms. XIST controls the inactivation of an entire X chromosome in female placental mammals. Here we develop and integrate several orthogonal structure-interaction methods to demonstrate that XIST RNA-protein complex folds into an evolutionarily conserved modular architecture. Chimeric RNAs and clustered protein binding in fRIP and eCLIP experiments align with long-range RNA secondary structure, revealing discrete XIST domains that interact with distinct sets of effector proteins. CRISPR-Cas9-mediated permutation of the Xist A-repeat location shows that A-repeat serves as a nucleation center for multiple Xist-associated proteins and m6A modification. Thus modular architecture plays an essential role, in addition to sequence motifs, in determining the specificity of RBP binding and m6A modification. Together, this work builds a comprehensive structure-function model for the XIST RNA-protein complex, and suggests a general strategy for mechanistic studies of large ribonucleoprotein assemblies.

scholarly journals Structural modularity of the XIST ribonucleoprotein complex

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhipeng Lu ◽  
Jimmy K. Guo ◽  
Yuning Wei ◽  
Diana R. Dou ◽  
Brian Zarnegar ◽  
...  
Keyword(s):  
Protein Complex ◽  
Protein Complexes ◽  
Effector Proteins ◽  
General Strategy ◽  
Sequence Motifs ◽  
Modular Architecture ◽  
Chimeric Rnas ◽  
Xist Rna ◽  
Evolutionarily Conserved ◽  
Associated Proteins

AbstractLong noncoding RNAs are thought to regulate gene expression by organizing protein complexes through unclear mechanisms. XIST controls the inactivation of an entire X chromosome in female placental mammals. Here we develop and integrate several orthogonal structure-interaction methods to demonstrate that XIST RNA-protein complex folds into an evolutionarily conserved modular architecture. Chimeric RNAs and clustered protein binding in fRIP and eCLIP experiments align with long-range RNA secondary structure, revealing discrete XIST domains that interact with distinct sets of effector proteins. CRISPR-Cas9-mediated permutation of the Xist A-repeat location shows that A-repeat serves as a nucleation center for multiple Xist-associated proteins and m6A modification. Thus modular architecture plays an essential role, in addition to sequence motifs, in determining the specificity of RBP binding and m6A modification. Together, this work builds a comprehensive structure-function model for the XIST RNA-protein complex, and suggests a general strategy for mechanistic studies of large ribonucleoprotein assemblies.

scholarly journals Human Ccr4–Not complexes contain variable deadenylase subunits

2009 ◽  
Vol 422 (3) ◽  
pp. 443-453 ◽  
Author(s):  
Nga-Chi Lau ◽  
Annemieke Kolkman ◽  
Frederik M. A. van Schaik ◽  
Klaas W. Mulder ◽  
W. W. M. Pim Pijnappel ◽  
...  
Keyword(s):  
Cell Lines ◽  
Mrna Synthesis ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Proteomic Approach ◽  
Core Proteins ◽  
Evolutionarily Conserved ◽  
Associated Proteins ◽  
Stable Core ◽  
Human Complex

The Ccr4–Not complex is evolutionarily conserved and important for regulation of mRNA synthesis and decay. The composition of the yeast complex has been well described. Orthologues of the yeast Ccr4–Not components have been identified in human cells including multiple subunits with mRNA deadenylase activity. In the present study, we examine the composition of the human Ccr4–Not complex in an in-depth proteomic approach using stable cell lines expressing tagged CNOT proteins. We find at least four different variants of the human complex, consisting of seven stable core proteins and mutually exclusive associated mRNA deadenylase subunits. Interestingly, human CNOT4 is in a separate ~200 kDa complex. Furthermore, analyses of associated proteins indicate involvement of Ccr4–Not complexes in splicing, transport and localization of RNA molecules. Taken together, human Ccr4–Not complexes are heterogeneous in composition owing to differences in their deadenylase subunits, which may reflect the multi-functionality of these complexes in cellular processes.

scholarly journals PPP1R35 is a novel centrosomal protein that regulates centriole length in concert with the microcephaly protein RTTN

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Andrew Michael Sydor ◽  
Etienne Coyaud ◽  
Cristina Rovelli ◽  
Estelle Laurent ◽  
Helen Liu ◽  
...  
Keyword(s):  
Live Cell Imaging ◽  
Cell Imaging ◽  
Super Resolution ◽  
Cellular Level ◽  
Mammalian Development ◽  
Centrosomal Protein ◽  
Associated Proteins ◽  
Bona Fide ◽  
Distal Centriole ◽  
Super Resolution Microscopy

Centrosome structure, function, and number are finely regulated at the cellular level to ensure normal mammalian development. Here, we characterize PPP1R35 as a novel bona fide centrosomal protein and demonstrate that it is critical for centriole elongation. Using quantitative super-resolution microscopy mapping and live-cell imaging we show that PPP1R35 is a resident centrosomal protein located in the proximal lumen above the cartwheel, a region of the centriole that has eluded detailed characterization. Loss of PPP1R35 function results in decreased centrosome number and shortened centrioles that lack centriolar distal and microtubule wall associated proteins required for centriole elongation. We further demonstrate that PPP1R35 acts downstream of, and forms a complex with, RTTN, a microcephaly protein required for distal centriole elongation. Altogether, our study identifies a novel step in the centriole elongation pathway centered on PPP1R35 and elucidates downstream partners of the microcephaly protein RTTN.

Sign in / Sign up

Export Citation Format

Share Document