title: The cytoskeletal protein RHAMM and ERK1/2 activity maintain the pluripotency of murine embryonic stem cells.
abstract: Receptor for hyaluronan mediated motility (RHAMM, encoded by HMMR) may be a cell-surface receptor for hyaluronan that regulates embryonic stem cell pluripotency and differentiation, however, a precise mechanism for its action is not known. We examined murine embryonic stem cells with and without hemizygous genomic mutation of Hmmr/RHAMM, but we were not able to find RHAMM on the cell-surface. Rather, RHAMM localized to the microtubule cytoskeleton and along mitotic spindles. Genomic loss of Hmmr/RHAMM did not alter cell cycle progression but augmented differentiation and attenuated pluripotency in murine embryonic stem cells. Through a candidate screen of small-molecule kinase inhibitors, we identified ERK1/2 and aurora kinase A as barrier kinases whose inhibition was sufficient to rescue pluripotency in RHAMM(+/-) murine embryonic stem cells. Thus, RHAMM is not found on the cell-surface of embryonic stem cells, but it is required to maintain pluripotency and its dominant mechanism of action is through the modulation of signal transduction pathways at microtubules.
authors.affiliation: Department of Pediatrics, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jihong
authors.initials: J
authors.lastname: Jiang
authors.forename: Pooja
authors.initials: P
authors.lastname: Mohan
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maxwell
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor
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