RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes Ludovic Jeanson, Bruno Copin, Jean-François.

Slides:

Advertisements

Similar presentations

Johanna Sigl-Glöckner, Michael Brecht Cell Reports

Advertisements

Loss-of-Function Mutations in RSPH1 Cause Primary Ciliary Dyskinesia with Central- Complex and Radial-Spoke Defects Esther Kott, Marie Legendre, Bruno.

Volume 125, Issue 5, Pages (November 2003)

Splice-Site Mutations in the Axonemal Outer Dynein Arm Docking Complex Gene CCDC114 Cause Primary Ciliary Dyskinesia Alexandros Onoufriadis, Tamara Paff,

Loss-of-Function Mutations in LRRC6, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms, Cause Primary Ciliary Dyskinesia Esther.

In Vivo Mechanisms of Vaccine-Induced Protection against HPV Infection

A Nonsense Mutation in the Human Homolog of Drosophila rogdi Causes Kohlschutter– Tonz Syndrome Adi Mory, Efrat Dagan, Barbara Illi, Philippe Duquesnoy,

Volume 35, Issue 2, Pages (October 2015)

A Corkscrew Model for Dynamin Constriction

CEP120 and SPICE1 Cooperate with CPAP in Centriole Elongation

A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa Goranka Tanackovic, Adriana Ransijn,

Transglutaminase 5 Expression in Human Hair Follicle

A Truncating Mutation of CEP135 Causes Primary Microcephaly and Disturbed Centrosomal Function Muhammad Sajid Hussain, Shahid Mahmood Baig, Sascha Neumann,

ASQ2 Encodes a TBCC-like Protein Required for Mother-Daughter Centriole Linkage and Mitotic Spindle Orientation Jessica L. Feldman, Wallace F. Marshall

Volume 11, Issue 2, Pages (February 2010)

Syndromic Short Stature in Patients with a Germline Mutation in the LIM Homeobox LHX4 Kalotina Machinis, Jacques Pantel, Irène Netchine, Juliane Léger,

TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization

Whole-Exome Capture and Sequencing Identifies HEATR2 Mutation as a Cause of Primary Ciliary Dyskinesia Amjad Horani, Todd E. Druley, Maimoona A. Zariwala,

Rose-Anne Romano, Barbara Birkaya, Satrajit Sinha

Knockdown of Myosin Va Isoforms by RNAi as a Tool to Block Melanosome Transport in Primary Human Melanocytes Mireille Van Gele, Barbara Geusens, Anne-Marie.

Protein Interaction Analysis Provides a Map of the Spatial and Temporal Organization of the Ciliary Gating Zone Daisuke Takao, Liang Wang, Allison Boss,

Mutations in C11orf70 Cause Primary Ciliary Dyskinesia with Randomization of Left/Right Body Asymmetry Due to Defects of Outer and Inner Dynein Arms

A Novel Keratin 5 Mutation (K5V186L) in a Family with EBS-K: a Conservative Substitution Can Lead to Development of Different Disease Phenotypes Mirjana.

The Bacterial Cytoskeleton

Volume 25, Issue 6, Pages (June 2017)

Toward a Molecular Structure of the Eukaryotic Kinetochore

Volume 24, Issue 22, Pages (November 2014)

The Wiskott-Aldrich syndrome

Mutations in DNAH1, which Encodes an Inner Arm Heavy Chain Dynein, Lead to Male Infertility from Multiple Morphological Abnormalities of the Sperm Flagella

Volume 27, Issue 1, Pages (July 2007)

Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects Tamara Paff, Niki T. Loges, Isabella Aprea, Kaman.

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility Tailai Chen, Yuehong Bian, Xiaoman Liu, Shigang Zhao, Keliang.

Johanna Sigl-Glöckner, Michael Brecht Cell Reports

Mutations in CSPP1 Lead to Classical Joubert Syndrome

Volume 15, Issue 20, Pages (October 2005)

D.R. Rich, A.L. Clark Osteoarthritis and Cartilage

Volume 20, Issue 1, Pages 9-19 (October 2005)

Michael R. Knowles, Margaret W. Leigh, Lawrence E

DNAI2 Mutations Cause Primary Ciliary Dyskinesia with Defects in the Outer Dynein Arm Niki Tomas Loges, Heike Olbrich, Lale Fenske, Huda Mussaffi, Judit.

Volume 23, Issue 9, Pages (September 2015)

Immunofluorescence staining of respiratory cells.

Volume 20, Issue 2, Pages (July 2017)

Autosomal-Dominant Woolly Hair Resulting from Disruption of Keratin 74 (KRT74), a Potential Determinant of Human Hair Texture Yutaka Shimomura, Muhammad.

The Graded Response to Sonic Hedgehog Depends on Cilia Architecture

Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause Primary Ciliary Dyskinesia and Male Infertility Elma El Khouri, Lucie Thomas, Ludovic Jeanson,

Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa Syndrome Fuxi Zhu, Fengsong Wang, Xiaoyu Yang, Jingjing Zhang, Huan Wu, Zhou.

Sharon F. Suchy, Robert L. Nussbaum

Volume 42, Issue 2, Pages e3 (July 2017)

A Corkscrew Model for Dynamin Constriction

Volume 26, Issue 3, Pages (May 2007)

Control of Centriole Length by CPAP and CP110

Mutations in FEZF1 Cause Kallmann Syndrome

Volume 15, Issue 3, Pages (September 2008)

Volume 23, Issue 9, Pages (September 2015)

Serum IgE Autoantibodies Target Keratinocytes in Patients with Atopic Dermatitis Sabine Altrichter, Ernst Kriehuber, Julia Moser, Rudolf Valenta, Tamara.

Aeri Cho, Masato Kato, Tess Whitwam, Ji Hoon Kim, Denise J. Montell

Apical localization of PKA fusion constructs in infected and fully differentiated human airway epithelial cells. Apical localization of PKA fusion constructs.

The Human Dermokine Gene: Description of Novel Isoforms with Different Tissue- Specific Expression and Subcellular Location Eve Toulza, Marie-Florence.

Deletions and Point Mutations of LRRC50 Cause Primary Ciliary Dyskinesia Due to Dynein Arm Defects Niki Tomas Loges, Heike Olbrich, Anita Becker-Heck,

Transmission electron micrographs of human airway cilia in transverse section of a) normal subjects, and examples of hallmark defects depicting b) the.

Fluorescence confocal micrograph images of human ciliated nasal epithelial cells showing presence (normal) or absence (examples here from different primary.

Segments R1, R3, R6 and R7, and GTPase activity of Mfn2ΔTM are necessary for mitochondrial fragmentation in COS7 cells. Segments R1, R3, R6 and R7, and.

Whole Exome Sequencing and Homozygosity Mapping Identify Mutation in the Cell Polarity Protein GPSM2 as the Cause of Nonsyndromic Hearing Loss DFNB82

Mutations in NEXN, a Z-Disc Gene, Are Associated with Hypertrophic Cardiomyopathy Hu Wang, Zhaohui Li, Jizheng Wang, Kai Sun, Qiqiong Cui, Lei Song, Yubao.

Ciliated cell expression of PKA fusion constructs in infected and fully differentiated human airway epithelial cells. Ciliated cell expression of PKA fusion.

Volume 15, Issue 5, Pages (May 2016)

Loss-of-Function Mutations in the Human Ortholog of Chlamydomonas reinhardtii ODA7 Disrupt Dynein Arm Assembly and Cause Primary Ciliary Dyskinesia Philippe.

Ciliary Abnormalities Due to Defects in the Retrograde Transport Protein DYNC2H1 in Short-Rib Polydactyly Syndrome Amy E. Merrill, Barry Merriman, Claire.

Loss-of-Function Mutations in a Human Gene Related to Chlamydomonas reinhardtii Dynein IC78 Result in Primary Ciliary Dyskinesia Gaëlle Pennarun, Estelle.

Loss of LKB1 Kinase Activity in Peutz-Jeghers Syndrome, and Evidence for Allelic and Locus Heterogeneity Hamid Mehenni, Corinne Gehrig, Jun-ichi Nezu,

Presentation transcript:

RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes Ludovic Jeanson, Bruno Copin, Jean-François Papon, Florence Dastot-Le Moal, Philippe Duquesnoy, Guy Montantin, Jacques Cadranel, Harriet Corvol, André Coste, Julie Désir, Anissa Souayah, Esther Kott, Nathalie Collot, Sylvie Tissier, Bruno Louis, Aline Tamalet, Jacques de Blic, Annick Clement, Estelle Escudier, Serge Amselem, Marie Legendre The American Journal of Human Genetics Volume 97, Issue 1, Pages 153-162 (July 2015) DOI: 10.1016/j.ajhg.2015.05.004 Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 1 CC/RS Defects in Respiratory Cilia of Individuals with RSPH3 Mutations (A) The electron micrographs of cross-sections of cilia from a control individual and five individuals with identified RSPH3 mutations are shown. For each affected individual, two sections are shown: one with a well-organized configuration (9+2) showing the presence of the CC but with a near absence of RSs (top) and another with an abnormal axonemal configuration (9+2 disorganized or 8+1 transposition) and no detectable RSs (bottom). Black scale bars represent 0.1 μm. (B) Distribution of the different ciliary defects (expressed as a percentage of abnormal cilia) identified by TEM in individuals with RSPH3 mutations. Reference values are those from the TEM study performed by Rossman et al. on 55 control (non-atopic non-smoker healthy) individuals: the proportion of cilia with a normal ultrastructure is 95.2% ± 3.5%, whereas that of cilia with a missing CC is 0.4% ± 0.8%.46 Abbreviations are as follows: IDA, inner dynein arms; ODA, outer dynein arms. The American Journal of Human Genetics 2015 97, 153-162DOI: (10.1016/j.ajhg.2015.05.004) Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 2 RSPH3 Mutations and Their Impact at the Protein Level in Individuals with PCD Exonic organization of the human RSPH3 cDNA containing the mutations for the five families described in this study (top). Domain-organization models of the corresponding protein (middle) and of the Chlamydomonas reinhardtii orthologous RSP3 (bottom) are also shown. The eight exons are indicated by empty or hashed boxes, which depict translated or untranslated sequences, respectively. According to the predictions by SMART and literature, RSPH3 is composed of a radial spoke 3 domain (RS3D, in red) containing an axoneme targeting domain (ATD, in yellow), a RIIa-domain-binding amphipathic helix (AHR, in blue), a Dpy-30-domain-binding amphipathic helix (AHD, in blue), three TQT-like LC8-binding motifs (T, in purple), two coil-coiled domains (CC, in green), and two phosphorylated threonines (P, orange circle). The American Journal of Human Genetics 2015 97, 153-162DOI: (10.1016/j.ajhg.2015.05.004) Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 3 Localization of RSPH3 and Other Ciliary Proteins in Airway Epithelial Cells from a Healthy Individual and Individual PCD9 RSPH3 (green) localized within cilia (red) of the airway epithelial cells of a healthy control (A–C) and was absent from the cilia of individual PCD9 (A′–C′). RSPH23 (D–F and D′–F′), RSPH1 (G–I and G′–I′), and RSPH4A (J–L and J′–L′) (all in green) localized within cilia (red) of the airway epithelial cells of a healthy control individual and of individual PCD9. RSPH11 (green) localized within cilia (red) of the airway epithelial cells of a healthy control individual (M–O) but was absent from the cilia of individual PCD9 (M′–O′). DNALI1 (P–R and P′–R′) (in green) localized within cilia (red) of the airway epithelial cells of a healthy control individual and of individual PCD9. Airway epithelial cells were examined after labeling with rabbit polyclonal antibodies directed against RSPH3 (Novus Biological NBP1-84244, 1:100, 37°C, 1 hr), RSPH23 (Sigma HPA044555, 1:200, 37°C, 1 hr), RSPH1 (Sigma HPA017382, 1:200, 37°C, 1 hr), RSPH4A (Sigma HPA031196, 1:200, 37°C, 1 hr), RSPH11 (Sigma HPA039193, 1:200, 37°C, 1 hr), or DNALI1 (Abcam ab87075, 1:400, 37°C, 1 hr) and a secondary goat anti-rabbit Alexa Fluor 488 (green) antibody (Invitrogen A11034). For control individuals, we used an antibody directed against acetylated α-tubulin (mouse monoclonal [6-11B-1], Abcam ab24610, 1:700) to visualize microtubules, revealed by a secondary goat anti-mouse Alexa Fluor 594 (red) antibody (Invitrogen A11032). Nuclei were stained with DAPI (Sigma 32670). White scale bars represent 10 μm. The American Journal of Human Genetics 2015 97, 153-162DOI: (10.1016/j.ajhg.2015.05.004) Copyright © 2015 The American Society of Human Genetics Terms and Conditions