Abstract
Hepatoma-derived growth factor-related proteins (HRP) comprise a family of 6 members, which the biological functions are still largely unclear. Here we show that during embryogenesis HRP-3 is strongly expressed in the developing nervous system. At early stages of development HRP-3 is located in the cytoplasm and neurites of cortical neurons. Upon maturation HRP-3 relocalizes continuously to the nuclei and in the majority of neurons of adult mice it is located exclusively in the nucleus. This redistribution from neurites to nuclei is also found in embryonic cortical neurons maturing in cell culture. We show that HRP-3 is necessary for proper neurite outgrowth in primary cortical neurons. To identify possible mechanisms of how HRP-3 modulate neuritogenesis we isolated HRP-3 interaction partners and demonstrate that it binds tubulin through the N-terminal so called HATH region, which is strongly conserved among members of the HRP family. It promotes tubulin polymerization, stabilizes and bundles microtubules. This activity depends on the extranuclear localization of HRP-3. HRP-3 thus could play an important role during neuronal development by its modulation of the neuronal cytoskeleton.
Highlights
Hepatoma-derived growth factor (HDGF) is a protein that was purified from secretions of hepatoma cells by virtue of its growth factor activity
We demonstrate that the protein locates to the cytoplasm and neurites during early nervous system development, whereas most of Hepatoma-derived growth factor-related proteins (HRP)-3 can be found in the nucleus in adult neurons
Because detailed data on the expression during prenatal development are not available, we investigated the embryonic HRP-3 expression pattern by using an HRP-3 specific affinity purified antibody on whole sections prepared from embryos at day 11.5 (E11.5) as well as transversal brain sections of embryos at E15.5
Summary
Hepatoma-derived growth factor (HDGF) is a protein that was purified from secretions of hepatoma cells by virtue of its growth factor activity. 5 M Taxol-stabilized microtubules were mixed with different concentrations of recombinant proteins in 25 l of tubulin polymerizing buffer and incubated for 30 min at 37 °C. At this time point neurites of cultured cells are strongly HRP-3 positive, whereas no or only little HRP-3 protein could be detected in the nuclear compartment (Fig. 2A).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
