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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Bibliographic Details
Published in:Molecular biology of the cell 2014-09, Vol.25 (18), p.2682-2694
Main Authors: Galletta, Brian J, Guillen, Rodrigo X, Fagerstrom, Carey J, Brownlee, Chris W, Lerit, Dorothy A, Megraw, Timothy L, Rogers, Gregory C, Rusan, Nasser M
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Basal Bodies - metabolism
Calmodulin - metabolism
Calmodulin-Binding Proteins
Cell Line
Centrioles - physiology
Drosophila melanogaster
Drosophila Proteins - metabolism
Male
Mechanotransduction, Cellular
Molecular Sequence Data
Neurons - physiology
Protein Interaction Domains and Motifs
Protein Transport
Sperm Motility
Spermatogenesis
Spermatozoa - physiology
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E13-10-0617