Rcd4 is a poorly characterized Drosophila centriole component whose mammalian counterpart, PPP1R35, is suggested to function in centriole elongation and conversion to centrosomes. Here, we show that rcd4 mutants exhibit fewer centrioles, aberrant mitoses, and reduced basal bodies in sensory organs. Rcd4 interacts with the C-terminal part of Ana3, which loads onto the procentriole during interphase, ahead of Rcd4 and before mitosis. Accordingly, depletion of Ana3 prevents Rcd4 recruitment but not vice versa. We find that neither Ana3 nor Rcd4 participates directly in the mitotic conversion of centrioles to centrosomes, but both are required to load Ana1, which is essential for such conversion. Whereas ana3 mutants are male sterile, reflecting a requirement for Ana3 for centriole development in the male germ line, rcd4 mutants are fertile and have male germ line centrioles of normal length. Thus, Rcd4 is essential in somatic cells but is not absolutely required in spermatogenesis, indicating tissue-specific roles in centriole and basal body formation.
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http://dx.doi.org/10.1083/jcb.201912154 | DOI Listing |
Nat Commun
May 2024
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
As daughter centrioles assemble during G2, they recruit conserved Ana3/RTTN followed by its partner Rcd4/PPP1R35. Together, this contributes to the subsequent recruitment of Ana1/CEP295, required for the centriole's conversion to a centrosome. Here, we show that Rcd4/PPP1R35 is also required to maintain 9-fold centriole symmetry in the Drosophila male germline; its absence causes microtubule triplets to disperse into a reduced number of doublet or singlet microtubules.
View Article and Find Full Text PDFmedRxiv
May 2023
Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
The principal barrier to an HIV cure is the presence of a latent viral reservoir (LVR) made up primarily of latently infected resting CD4+ (rCD4) T-cells. Studies in the United States have shown that the LVR decays slowly (half-life=3.8 years), but this rate in African populations has been understudied.
View Article and Find Full Text PDFiScience
January 2023
UNC HIV Cure Center, Institute of Global Health and Infectious Diseases, the University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7042, USA.
HIV reservoirs are extremely stable and pose a tremendous challenge to clear HIV infection. Here, we demonstrate that activation of ISR/ATF4 signaling reverses HIV latency, which also selectively eliminates HIV+ cells in primary CD4T cell model of latency without effect on HIV-negative CD4T cells. The reduction of HIV+ cells is associated with apoptosis enhancement, but surprisingly is largely seen in HIV-infected cells in which gag-pol RNA transcripts are detected in HIV RNA-induced ATF4/IFIT signaling.
View Article and Find Full Text PDFInt J Mol Sci
October 2022
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
Unidentified pathogenetic mechanisms and genetic and clinical heterogeneity represent critical factors hindering the development of treatments for inherited retinal dystrophies. Frameshift mutations in , which codes for an accessory subunit of voltage-gated calcium channels (VGCC), cause cone-rod dystrophy RCD4 in patients, but the underlying mechanisms remain unknown. To define its pathogenetic mechanisms, we investigated the impact of a frameshift mutation on the electrophysiological profile and calcium handling of mouse rod photoreceptors by patch-clamp recordings and calcium imaging, respectively.
View Article and Find Full Text PDFJ Cell Biol
April 2021
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
The centrosome is the main microtubule-organizing center in animal cells. It comprises of two centrioles and the surrounding pericentriolar material. Protein organization at the outer layer of the centriole and outward has been studied extensively; however, an overall picture of the protein architecture at the centriole core has been missing.
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