Abstract
Bipolar spindle assembly is necessary to ensure the proper progression of cell division. Loss of spindle pole integrity leads to multipolar spindles and aberrant chromosomal segregation. However, the mechanism underlying the maintenance of spindle pole integrity remains unclear. In this study, we show that the actin‐binding protein adducin‐1 (ADD1) is phosphorylated at S726 during mitosis. S726‐phosphorylated ADD1 localizes to centrosomes, wherein it organizes into a rosette‐like structure at the pericentriolar material. ADD1 depletion causes centriole splitting and therefore results in multipolar spindles during mitosis, which can be restored by re‐expression of ADD1 and the phosphomimetic S726D mutant but not by the S726A mutant. Moreover, the phosphorylation of ADD1 at S726 is crucial for its interaction with TPX2, which is essential for spindle pole integrity. Together, our findings unveil a novel function of ADD1 in maintaining spindle pole integrity through its interaction with TPX2.
Highlights
To achieve faithful chromosome segregation, a bipolar spindle has to be established
The phosphorylation level of ADD1 at S726 was increased in the M phase, but it returned to the baseline upon cell cycle progression to the G1 phase, as analyzed by immunoblotting with an antibody specific to S726-phosphorylated ADD1 (Fig 1A)
How do cells keep the integrity of spindle pole under such forces? One of the mechanisms may be via a process called centrosome maturation, which occurs at the onset of mitosis and is characterized by pericentriolar materials (PCMs) expansion via the recruitment of PCM proteins, such as PCNT and c-tubulin, to centrosomes [45,46]
Summary
To achieve faithful chromosome segregation, a bipolar spindle has to be established. Correct reproduction and structural organization of centrosomes are crucial for the establishment of spindle bipolarity [1,2]. Multipolar spindles are often seen in human tumors and are usually associated with multiple centrosomes and chromosomal instability [3]. Centrosome overduplication and cytokinesis failure lead to multiple centrosomes and multipolar spindles [4]. Multipolar spindles can result from the loss of spindle pole integrity. Each bipolar spindle pole or centrosome consists of engaged mother and daughter centrioles surrounded by organized pericentriolar materials (PCMs) [5]. The loss of spindle pole integrity can lead to PCM fragmentation or centriole splitting, resulting in excess centrosomes and multipolar spindles during mitosis [6]
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