RHAMM is a centrosomal protein that interacts with dynein and maintains spindle pole stability.
The receptor for hyaluronan-mediated motility (RHAMM), an acidic coiled coil protein, has previously been characterized as a cell surface receptor for hyaluronan, and a microtubule-associated intracellular hyaluronan binding protein. In this study, we demonstrate that a subset of cellular RHAMM localizes to the centrosome and functions in the maintenance of spindle integrity. We confirm a previous study showing that the amino terminus of RHAMM interacts with microtubules and further demonstrate that a separate carboxy-terminal domain is required for centrosomal targeting. This motif overlaps the defined hyaluronan binding domain and bears 72% identity to the dynein interaction domain of Xklp2. RHAMM antibodies coimmunprecipitate dynein IC from Xenopus and HeLa extracts. Deregulation of RHAMM expression inhibits mitotic progression and affects spindle architecture. Structure, localization, and function, along with phylogenetic analysis, suggests that RHAMM may be a new member of the TACC family. Thus, we demonstrate a novel centrosomal localization and mitotic spindle-stabilizing function for RHAMM. Moreover, we provide a potential mechanism for this function in that RHAMM may cross-link centrosomal microtubules, through a direct interaction with microtubules and an association with dynein.
Maxwell
Christopher A
CA
Department of Oncology, University of Alberta/Cross Cancer Institute, Edmonton Alberta Canada T6G 1Z2.
Keats
Jonathan J
JJ
Crainie
Mary
M
Sun
Xuejun
X
Yen
Tim
T
Shibuya
Ellen
E
Hendzel
Michael
M
Chan
Gordon
G
Pilarski
Linda M
LM
D018385:Centrosome / Q000378:metabolism*; D002874:Chromosome Mapping; D004398:Dyneins / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007399:Interphase / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D010802:Phylogeny; D008941:Spindle Apparatus / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor; D004398:Dyneins