XRHAMM Functions in Ran-Dependent Microtubule Nucleation and Pole Formation during Anastral Spindle Assembly

• Published in: Current biology Vol. 14; no. 20; pp. 1801 - 1811
• Main Authors: Groen, Aaron C., Cameron, Lisa A., Coughlin, Margaret, Miyamoto, David T., Mitchison, Timothy J., Ohi, Ryoma
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 26.10.2004
• Subjects: Animals; Base Sequence; Cell Cycle Proteins - metabolism; Centrosome - metabolism; Chromatography, Liquid; DNA Primers; Fluorescent Antibody Technique; Immunoblotting; Mass Spectrometry; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; Molecular Sequence Data; Neoplasm Proteins - metabolism; Nuclear Proteins - metabolism; Phosphoproteins - metabolism; Plasmids - genetics; ran GTP-Binding Protein - metabolism; Sequence Analysis, DNA; Spindle Apparatus - metabolism; Xenopus; Xenopus Proteins - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2004.10.002

Background: The regulated assembly of microtubules is essential for bipolar spindle formation. Depending on cell type, microtubules nucleate through two different pathways: centrosome-driven or chromatin-driven. The chromatin-driven pathway dominates in cells lacking centrosomes. Results: Human RHAMM (receptor for hyaluronic-acid-mediated motility) was originally implicated in hyaluronic-acid-induced motility but has since been shown to associate with centrosomes and play a role in astral spindle pole integrity in mitotic systems. We have identified the Xenopus ortholog of human RHAMM as a microtubule-associated protein that plays a role in focusing spindle poles and is essential for efficient microtubule nucleation during spindle assembly without centrosomes. XRHAMM associates both with γ-TuRC, a complex required for microtubule nucleation and with TPX2, a protein required for microtubule nucleation and spindle pole organization. Conclusions: XRHAMM facilitates Ran-dependent, chromatin-driven nucleation in a process that may require coordinate activation of TPX2 and γ-TuRC.