Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782334570748706816 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4161505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT gallettabrianj drosophilapericentrinrequiresinteractionwithcalmodulinforitsfunctionatcentrosomesandneuronalbasalbodiesbutnotatspermbasalbodies AT guillenrodrigox drosophilapericentrinrequiresinteractionwithcalmodulinforitsfunctionatcentrosomesandneuronalbasalbodiesbutnotatspermbasalbodies AT fagerstromcareyj drosophilapericentrinrequiresinteractionwithcalmodulinforitsfunctionatcentrosomesandneuronalbasalbodiesbutnotatspermbasalbodies AT brownleechrisw drosophilapericentrinrequiresinteractionwithcalmodulinforitsfunctionatcentrosomesandneuronalbasalbodiesbutnotatspermbasalbodies AT leritdorothya drosophilapericentrinrequiresinteractionwithcalmodulinforitsfunctionatcentrosomesandneuronalbasalbodiesbutnotatspermbasalbodies AT megrawtimothyl drosophilapericentrinrequiresinteractionwithcalmodulinforitsfunctionatcentrosomesandneuronalbasalbodiesbutnotatspermbasalbodies AT rogersgregoryc drosophilapericentrinrequiresinteractionwithcalmodulinforitsfunctionatcentrosomesandneuronalbasalbodiesbutnotatspermbasalbodies AT rusannasserm drosophilapericentrinrequiresinteractionwithcalmodulinforitsfunctionatcentrosomesandneuronalbasalbodiesbutnotatspermbasalbodies |