Mob4 is essential for spermatogenesis in Drosophila melanogaster

Santos, Inês B.; Wainman, Alan; Garrido-Maraver, Juan; Pires, Vanessa; Riparbelli, Maria Giovanna; Kovács, Levente; Callaini, Giuliano; Glover, David M.; Tavares, Álvaro A.; Jafar-Nejad, ed., H.

doi:10.1093/genetics/iyad104

Title: Mob4 is essential for spermatogenesis in Drosophila melanogaster

Journal Article · 31 May 2023 · Genetics (Online)

DOI: https://doi.org/10.1093/genetics/iyad104 · OSTI ID:1994421

Santos, Inês B.; Wainman, Alan; Garrido-Maraver, Juan; Pires, Vanessa; Riparbelli, Maria Giovanna; Kovács, Levente; Callaini, Giuliano; Glover, David M.; Tavares, Álvaro A.; Jafar-Nejad, ed., H.

Abstract Gamete formation is essential for sexual reproduction in metazoans. Meiosis in males gives rise to spermatids that must differentiate and individualize into mature sperm. In Drosophila melanogaster, individualization of interconnected spermatids requires the formation of individualization complexes that synchronously move along the sperm bundles. Here, we show that Mob4, a member of the Mps-one binder family, is essential for male fertility but has no detectable role in female fertility. We show that Mob4 is required for proper axonemal structure and its loss leads to male sterility associated with defective spermatid individualization and absence of mature sperm in the seminal vesicles. Transmission electron micrographs of developing spermatids following mob4RNAi revealed expansion of the outer axonemal microtubules such that the 9 doublets no longer remained linked to each other and defective mitochondrial organization. Mob4 is a STRIPAK component, and male fertility is similarly impaired upon depletion of the STRIPAK components, Strip and Cka. Expression of the human Mob4 gene rescues all phenotypes of Drosophila mob4 downregulation, indicating that the gene is evolutionarily and functionally conserved. Together, this suggests that Mob4 contributes to the regulation of the microtubule- and actin-cytoskeleton during spermatogenesis through the conserved STRIPAK complex. Our study advances the understanding of male infertility by uncovering the requirement for Mob4 in sperm individualization.

View Journal Article

Cite

Export

Save

Sponsoring Organization:: USDOE Office of Nuclear Energy (NE), Nuclear Fuel Cycle and Supply Chain

OSTI ID:: 1994421

Journal Information:: Genetics (Online), Journal Name: Genetics (Online) Journal Issue: 4 Vol. 224; ISSN 1943-2631

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

References (42)

Genetic control of cell proliferation and differentiation inDrosophilaspermatogenesis Fuller, Margaret T. Seminars in Cell & Developmental Biology, Vol. 9, Issue 4 https://doi.org/10.1006/scdb.1998.0227	journal	August 1998
Affinity Purification of Protein Complexes from Drosophila Embryos in Cell Cycle Studies Lipinszki, Zoltan; Wang, Peng; Grant, Rhys Methods in Molecular Biology https://doi.org/10.1007/978-1-4939-0888-2_33	book	January 2014
Dynamics of spermiogenesis in Drosophila melanogaster Tokuyasu, K. T.; Peacock, W. J.; Hardy, R. W. Zeitschrift f�r Zellforschung und Mikroskopische Anatomie, Vol. 124, Issue 4 https://doi.org/10.1007/BF00335253	journal	January 1972
Disorders of spermatogenesis Tüttelmann, Frank; Ruckert, Christian; Röpke, Albrecht Medizinische Genetik, Vol. 30, Issue 1 https://doi.org/10.1007/s11825-018-0181-7	journal	February 2018
STRIPAK complexes: Structure, biological function, and involvement in human diseases Hwang, Juyeon; Pallas, David C. The International Journal of Biochemistry & Cell Biology, Vol. 47 https://doi.org/10.1016/j.biocel.2013.11.021	journal	February 2014
Evolutionary Divergence of Enzymatic Mechanisms for Posttranslational Polyglycylation Rogowski, Krzysztof; Juge, François; van Dijk, Juliette Cell, Vol. 137, Issue 6 https://doi.org/10.1016/j.cell.2009.05.020	journal	June 2009
Homeostatic Control of Hpo/MST Kinase Activity through Autophosphorylation-Dependent Recruitment of the STRIPAK PP2A Phosphatase Complex Zheng, Yonggang; Liu, Bo; Wang, Li Cell Reports, Vol. 21, Issue 12 https://doi.org/10.1016/j.celrep.2017.11.076	journal	December 2017
Sustained Elongation of Sperm Tail Promoted by Local Remodeling of Giant Mitochondria in Drosophila Noguchi, Tatsuhiko; Koizumi, Michiko; Hayashi, Shigeo Current Biology, Vol. 21, Issue 10 https://doi.org/10.1016/j.cub.2011.04.016	journal	May 2011
Wampa is a dynein subunit required for axonemal assembly and male fertility in Drosophila Bauerly, Elisabeth; Yi, Kexi; Gibson, Matthew C. Developmental Biology, Vol. 463, Issue 2 https://doi.org/10.1016/j.ydbio.2020.04.006	journal	July 2020
Caspase Activity and a Specific Cytochrome C Are Required for Sperm Differentiation in Drosophila Arama, Eli; Agapite, Julie; Steller, Hermann Developmental Cell, Vol. 4, Issue 5 https://doi.org/10.1016/s1534-5807(03)00120-5	journal	May 2003
Drosophila Strip serves as a platform for early endosome organization during axon elongation Sakuma, Chisako; Kawauchi, Takeshi; Haraguchi, Shuka Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms6180	journal	October 2014
NIH Image to ImageJ: 25 years of image analysis Schneider, Caroline A.; Rasband, Wayne S.; Eliceiri, Kevin W. Nature Methods, Vol. 9, Issue 7 https://doi.org/10.1038/nmeth.2089	journal	June 2012
STRIPAK integrates upstream signals to initiate the Hippo kinase cascade Chen, Rui; Xie, Ruiling; Meng, Zhipeng Nature Cell Biology, Vol. 21, Issue 12 https://doi.org/10.1038/s41556-019-0426-y	journal	December 2019
Cryo-EM structure of the Hippo signaling integrator human STRIPAK Jeong, Byung-Cheon; Bae, Sung Jun; Ni, Lisheng Nature Structural & Molecular Biology, Vol. 28, Issue 3 https://doi.org/10.1038/s41594-021-00564-y	journal	February 2021
The MST4–MOB4 complex disrupts the MST1–MOB1 complex in the Hippo–YAP pathway and plays a pro-oncogenic role in pancreatic cancer Chen, Min; Zhang, Hui; Shi, Zhubing Journal of Biological Chemistry, Vol. 293, Issue 37 https://doi.org/10.1074/jbc.RA118.003279	journal	August 2018
A PP2A Phosphatase High Density Interaction Network Identifies a Novel Striatin-interacting Phosphatase and Kinase Complex Linked to the Cerebral Cavernous Malformation 3 (CCM3) Protein Goudreault, Marilyn; D’Ambrosio, Lisa M.; Kean, Michelle J. Molecular & Cellular Proteomics, Vol. 8, Issue 1 https://doi.org/10.1074/mcp.M800266-MCP200	journal	September 2008
Phocein: A potential actor in vesicular trafficking at Purkinje cell dendritic spines Bailly, Yannick J. R.; Castets, Francis The Cerebellum, Vol. 6, Issue 4 https://doi.org/10.1080/14734220701225912	journal	December 2007
Two Drosophila beta tubulin isoforms are not functionally equivalent. Hoyle, H. D.; Raff, E. C. Journal of Cell Biology, Vol. 111, Issue 3 https://doi.org/10.1083/jcb.111.3.1009	journal	September 1990
A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation Neisch, Amanda L.; Neufeld, Thomas P.; Hays, Thomas S. Journal of Cell Biology, Vol. 216, Issue 2 https://doi.org/10.1083/jcb.201606082	journal	January 2017
Molecular Cloning and Characterization of Phocein, a Protein Found from the Golgi Complex to Dendritic Spines Baillat, Gilbert; Moqrich, Abdelaziz; Castets, Francis Molecular Biology of the Cell, Vol. 12, Issue 3 https://doi.org/10.1091/mbc.12.3.663	journal	March 2001
Interacting genes that affect microtubule function in Drosophila melanogaster: two classes of mutation revert the failure to complement between haync2 and mutations in tubulin genes. Regan, C. L.; Fuller, M. T. Genetics, Vol. 125, Issue 1 https://doi.org/10.1093/genetics/125.1.77	journal	May 1990
The Drosophila clathrin heavy chain gene: clathrin function is essential in a multicellular organism. Bazinet, C.; Katzen, A. L.; Morgan, M. Genetics, Vol. 134, Issue 4 https://doi.org/10.1093/genetics/134.4.1119	journal	August 1993
FlyBase: a guided tour of highlighted features Gramates, L. Sian; Agapite, Julie; Attrill, Helen Genetics, Vol. 220, Issue 4 https://doi.org/10.1093/genetics/iyac035	journal	March 2022
FlyAtlas 2 in 2022: enhancements to the Drosophila melanogaster expression atlas Krause, Sue A.; Overend, Gayle; Dow, Julian A. T. Nucleic Acids Research, Vol. 50, Issue D1 https://doi.org/10.1093/nar/gkab971	journal	October 2021
Protein Interaction Network of the Mammalian Hippo Pathway Reveals Mechanisms of Kinase-Phosphatase Interactions Couzens, A. L.; Knight, J. D. R.; Kean, M. J. Science Signaling, Vol. 6, Issue 302 https://doi.org/10.1126/scisignal.2004712	journal	November 2013
CKA, a Novel Multidomain Protein, Regulates the JUN N-Terminal Kinase Signal Transduction Pathway in Drosophila Chen, Hua-Wei; Marinissen, Maria Julia; Oh, Su-Wan Molecular and Cellular Biology, Vol. 22, Issue 6 https://doi.org/10.1128/MCB.22.6.1792-1803.2002	journal	March 2002
Bug22 influences cilium morphology and the post-translational modification of ciliary microtubules Mendes Maia, Teresa; Gogendeau, Delphine; Pennetier, Carole Biology Open, Vol. 3, Issue 2 https://doi.org/10.1242/bio.20146577	journal	January 2014
The Drosophila fusome, a germline-specific organelle, contains membrane skeletal proteins and functions in cyst formation Lin, Haifan; Yue, Lin; Spradling, Allan C. Development, Vol. 120, Issue 4 https://doi.org/10.1242/dev.120.4.947	journal	April 1994
Genetic dissection of sperm individualization in Drosophila melanogaster Fabrizio, James J.; Hime, Gary; Lemmon, Sandra K. Development, Vol. 125, Issue 10 https://doi.org/10.1242/dev.125.10.1833	journal	May 1998
StripandCkanegatively regulate JNK signalling duringDrosophilaspermatogenesis La Marca, John E.; Diepstraten, Sarah T.; Hodge, Amy Development https://doi.org/10.1242/dev.174292	journal	January 2019
Mob4 plays a role in spindle focusing in Drosophila S2 cells Trammell, Matthew A.; Mahoney, Nicole M.; Agard, David A. Journal of Cell Science, Vol. 121, Issue 8 https://doi.org/10.1242/jcs.017210	journal	April 2008
Mob4-dependent STRIPAK involves the chaperonin TRiC to coordinate myofibril and microtubule network growth Berger, Joachim; Berger, Silke; Currie, Peter D. PLOS Genetics, Vol. 18, Issue 6 https://doi.org/10.1371/journal.pgen.1010287	journal	June 2022
The TRiC/CCT Chaperone Is Implicated in Alzheimer's Disease Based on Patient GWAS and an RNAi Screen in Aβ-Expressing Caenorhabditis elegans Khabirova, Eleonora; Moloney, Aileen; Marciniak, Stefan J. PLoS ONE, Vol. 9, Issue 7 https://doi.org/10.1371/journal.pone.0102985	journal	July 2014
Testis-Specific Bb8 Is Essential in the Development of Spermatid Mitochondria Vedelek, Viktor; Laurinyecz, Barbara; Kovács, Attila L. PLOS ONE, Vol. 11, Issue 8 https://doi.org/10.1371/journal.pone.0161289	journal	August 2016
QuickFigures: A toolkit and ImageJ PlugIn to quickly transform microscope images into scientific figures Mazo, Gregory PLOS ONE, Vol. 16, Issue 11 https://doi.org/10.1371/journal.pone.0240280	journal	November 2021
DMob4/Phocein Regulates Synapse Formation, Axonal Transport, and Microtubule Organization Schulte, Joost; Sepp, Katharine J.; Jorquera, Ramon A. The Journal of Neuroscience, Vol. 30, Issue 15 https://doi.org/10.1523/JNEUROSCI.5823-09.2010	journal	April 2010
Molecular mechanisms of gene regulation during Drosophila spermatogenesis White-Cooper, Helen REPRODUCTION, Vol. 139, Issue 1 https://doi.org/10.1530/REP-09-0083	journal	January 2010
A Drosophila toolkit for defining gene function in spermatogenesis Siddall, N. A.; Hime, G. R. Reproduction, Vol. 153, Issue 4 https://doi.org/10.1530/REP-16-0347	journal	April 2017
The BDGP Gene Disruption Project Bellen, Hugo J.; Levis, Robert W.; Liao, Guochun Genetics, Vol. 167, Issue 2 https://doi.org/10.1534/genetics.104.026427	journal	June 2004
Highly Specific and Efficient CRISPR/Cas9-Catalyzed Homology-Directed Repair in Drosophila Gratz, Scott J.; Ukken, Fiona P.; Rubinstein, C. Dustin Genetics, Vol. 196, Issue 4 https://doi.org/10.1534/genetics.113.160713	journal	April 2014
Mob4 is required for neurodevelopment in zebrafish Florindo, Claudia; Mimoso, Jorge M.; Palma, Sandra L. microPublication Biology https://doi.org/10.17912/micropub.biology.000762	datapaper	January 2023
SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK Bae, Sung Jun; Ni, Lisheng; Osinski, Adam eLife, Vol. 6 https://doi.org/10.7554/eLife.30278	journal	October 2017

Similar Records

THE NATURE OF THE DEPENDENCE RELATION OF THE FREQUENCY OF LETHALS ARISING AT DIFFERENT STAGES OF SPERMATOGENESIS ON THE DOSE OF X-RAYS

Journal Article · 1959 · Doklady Akad. Nauk S.S.S.R. · OSTI ID:4288976

Belgovskii, M L; Abeleva, E A; Potekhina, N A

The Cell Cycle Timing of Centromeric Chromatin Assembly in Drosophila Meiosis Is Distinct from Mitosis Yet Requires CAL1 and CENP-C

Journal Article · 2012 · PLoS Biology (Online) · OSTI ID:1627168

Dunleavy, Elaine M.; Beier, Nicole L.; Gorgescu, Walter; +3 more

DEVELOPMENTAL-GENETIC STUDY OF THE EFFECTS OF X-RAY IRRADIATION IN DROSOPHILA VIRILIS AND BUFO VALLICEPS. Final Scientific Report, January 1, 1955-December 31, 1960

Technical Report · 1961 · OSTI ID:4067768

Clayton, F E

Title: Mob4 is essential for spermatogenesis in Drosophila melanogaster

Citation Formats

References (42)

Similar Records

Related Subjects