期刊
JOURNAL OF CELL SCIENCE
卷 125, 期 16, 页码 3745-3751出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.105130
关键词
NEDD1; Spindle; Phosphorylation; Y-tubulin; Mitosis; CEP192
类别
资金
- Canadian Cancer Society [019562]
- Fundacion Caja Madrid
During cell division, microtubules organize a bipolar spindle to drive accurate chromosome segregation to daughter cells. Microtubules are nucleated by the gamma-TuRC, a gamma-tubulin complex that acts as a template for microtubules with 13 protofilaments. Cells lacking gamma-TuRC core components do nucleate microtubules; however, these polymers fail to form bipolar spindles. NEDD1 is a gamma-TuRC-interacting protein whose depletion, although not affecting gamma-TuRC stability, causes spindle defects similar to the inhibition of its core subunits, including gamma-tubulin. Several residues of NEDD1 are phosphorylated in mitosis. However, previously identified phosphorylation sites only partially regulate NEDD1 function, as NEDD1 depletion has a much stronger phenotype than mutation of these residues. Using mass spectrometry, we have identified multiple novel phosphorylated sites in the serine (S) 557-S574 region of NEDD1, close to its gamma-tubulin-binding domain. Serine to alanine mutations in S565-S574 inhibit the binding of NEDD1 to gamma-tubulin and perturb NEDD1 mitotic function, yielding microtubule organization defects equivalent to those observed in NEDD1-depleted cells. Interestingly, additional mutations in the S557-T560 region restore the capacity of NEDD1 to bind gamma-tubulin and promote bipolar spindle assembly. All together, our data suggest that the NEDD1/gamma-tubulin interaction is finely tuned by multiple phosphorylation events in the S557-S574 region and is critical for spindle assembly. We also found that CEP192, a centrosomal protein similarly required for spindle formation, associates with NEDD1 and modulates its mitotic phosphorylation. Thus CEP192 may regulate spindle assembly by modulating NEDD1 function.
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