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Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies

Pericentrin is a critical centrosomal protein required for organizing pericentriolar material (PCM) in mitosis. Mutations in pericentrin cause the human genetic disorder Majewski/microcephalic osteodysplastic primordial dwarfism type II, making a detailed understanding of its regulation extremely im...

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Autores principales: Galletta, Brian J., Guillen, Rodrigo X., Fagerstrom, Carey J., Brownlee, Chris W., Lerit, Dorothy A., Megraw, Timothy L., Rogers, Gregory C., Rusan, Nasser M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161505/
https://www.ncbi.nlm.nih.gov/pubmed/25031429
http://dx.doi.org/10.1091/mbc.E13-10-0617
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author Galletta, Brian J.
Guillen, Rodrigo X.
Fagerstrom, Carey J.
Brownlee, Chris W.
Lerit, Dorothy A.
Megraw, Timothy L.
Rogers, Gregory C.
Rusan, Nasser M.
author_facet Galletta, Brian J.
Guillen, Rodrigo X.
Fagerstrom, Carey J.
Brownlee, Chris W.
Lerit, Dorothy A.
Megraw, Timothy L.
Rogers, Gregory C.
Rusan, Nasser M.
author_sort Galletta, Brian J.
collection PubMed
description Pericentrin is a critical centrosomal protein required for organizing pericentriolar material (PCM) in mitosis. Mutations in pericentrin cause the human genetic disorder Majewski/microcephalic osteodysplastic primordial dwarfism type II, making a detailed understanding of its regulation extremely important. Germaine to pericentrin's function in organizing PCM is its ability to localize to the centrosome through the conserved C-terminal PACT domain. Here we use Drosophila pericentrin-like-protein (PLP) to understand how the PACT domain is regulated. We show that the interaction of PLP with calmodulin (CaM) at two highly conserved CaM-binding sites in the PACT domain controls the proper targeting of PLP to the centrosome. Disrupting the PLP-CaM interaction with single point mutations renders PLP inefficient in localizing to centrioles in cultured S2 cells and Drosophila neuroblasts. Although levels of PCM are unaffected, it is highly disorganized. We also demonstrate that basal body formation in the male testes and the production of functional sperm does not rely on the PLP-CaM interaction, whereas production of functional mechanosensory neurons does.
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spelling pubmed-41615052014-11-30 Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies Galletta, Brian J. Guillen, Rodrigo X. Fagerstrom, Carey J. Brownlee, Chris W. Lerit, Dorothy A. Megraw, Timothy L. Rogers, Gregory C. Rusan, Nasser M. Mol Biol Cell Articles Pericentrin is a critical centrosomal protein required for organizing pericentriolar material (PCM) in mitosis. Mutations in pericentrin cause the human genetic disorder Majewski/microcephalic osteodysplastic primordial dwarfism type II, making a detailed understanding of its regulation extremely important. Germaine to pericentrin's function in organizing PCM is its ability to localize to the centrosome through the conserved C-terminal PACT domain. Here we use Drosophila pericentrin-like-protein (PLP) to understand how the PACT domain is regulated. We show that the interaction of PLP with calmodulin (CaM) at two highly conserved CaM-binding sites in the PACT domain controls the proper targeting of PLP to the centrosome. Disrupting the PLP-CaM interaction with single point mutations renders PLP inefficient in localizing to centrioles in cultured S2 cells and Drosophila neuroblasts. Although levels of PCM are unaffected, it is highly disorganized. We also demonstrate that basal body formation in the male testes and the production of functional sperm does not rely on the PLP-CaM interaction, whereas production of functional mechanosensory neurons does. The American Society for Cell Biology 2014-09-15 /pmc/articles/PMC4161505/ /pubmed/25031429 http://dx.doi.org/10.1091/mbc.E13-10-0617 Text en © 2014 Galletta, Guillen, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Galletta, Brian J.
Guillen, Rodrigo X.
Fagerstrom, Carey J.
Brownlee, Chris W.
Lerit, Dorothy A.
Megraw, Timothy L.
Rogers, Gregory C.
Rusan, Nasser M.
Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies
title Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies
title_full Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies
title_fullStr Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies
title_full_unstemmed Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies
title_short Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies
title_sort drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161505/
https://www.ncbi.nlm.nih.gov/pubmed/25031429
http://dx.doi.org/10.1091/mbc.E13-10-0617
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