Tubulin nucleotide status controls Sas-4-dependent pericentriolar material recruitment.
Regulated centrosome biogenesis is required for accurate cell division and for maintaining genome integrity. Centrosomes consist of a centriole pair surrounded by a protein network known as pericentriolar material (PCM). PCM assembly is a tightly regulated, critical step that determines the size and capability of centrosomes. Here, we report a role for tubulin in regulating PCM recruitment through the conserved centrosomal protein Sas-4. Tubulin directly binds to Sas-4; together they are components of cytoplasmic complexes of centrosomal proteins. A Sas-4 mutant, which cannot bind tubulin, enhances centrosomal protein complex formation and has abnormally large centrosomes with excessive activity. These results suggest that tubulin negatively regulates PCM recruitment. Whereas tubulin-GTP prevents Sas-4 from forming protein complexes, tubulin-GDP promotes it. Thus, the regulation of PCM recruitment by tubulin depends on its GTP/GDP-bound state. These results identify a role for tubulin in regulating PCM recruitment independent of its well-known role as a building block of microtubules. On the basis of its guanine-bound state, tubulin can act as a molecular switch in PCM recruitment.
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jayachandran
J
Gopalakrishnan
Yiu-Cheung Frederick
YC
Chim
Andrew
A
Ha
Marcus L
ML
Basiri
Dorothy A
DA
Lerit
Nasser M
NM
Rusan
Tomer
T
Avidor-Reiss
D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002502:Centrioles; D018385:Centrosome / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005812:Genes, Switch; D008869:Microtubule-Associated Proteins; D009711:Nucleotides / Q000737:chemistry / Q000235:genetics; D009929:Organ Size; D011485:Protein Binding; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism*
D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D009711:Nucleotides; C522063:Sas-4 protein, Drosophila; D014404:Tubulin