Demonstration of a ubiquitin binding site on murine haemopoietic progenitor cells: implication of ubiquitin in homing and adhesion

Summary. Investigations into the nature of the molecular interactions mediating the recognition of the haemopoietic progenitor cells by the haemopoietic stroma, indicate that ubiquitin mediates the binding between murine haemopoietic progenitors and the haemopoietic stroma. The adhesion of haemopoietic progenitors to anti-ubiquitin antibody treated bone marrow stromal cultures, shows inhibition of binding by approximately 78%. Affinity purification of the 1% Triton X-100 soluble stromal membrane fraction, on anti-ubiquitin-sepharose revealed a ubiquitinated 55 kD subunit. Progenitor cells treated with ubiquitin show approximately 58% inhibition in their ability to home into spleen, indicating the direct involvement of ubiquitin in homing. Histochemical staining of bone marrow cells using ubiquitin as a probe further delineates a population of cells possessing specific binding sites for ubiquitin. We demonstrate here the presence of a ubiquitin binding site on the haemopoietic progenitor cells, which may play a major role in the targeting of such progenitors to their 'niche' within the haemopoietic tissue. Such ubiquitin-mediated recognition may thus constitute a common molecular mechanism for homing and adhesion to both bone marrow and spleen, and may be implicated in the homing of more primitive, less differentiated haemopoietic progenitors. The results also indicate that the homing of haemopoietic progenitors within the haemopoietic micro-environment may be mediated by both a ubiquitin dependent and another ubiquitin independent mechanism.