Hepatoma-derived growth factor-related protein-3 interacts with microtubules and promotes neurite outgrowth in mouse cortical neurons.
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.
El-Tahir
Heba M
HM
Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms Universität, Nussallee 11, 53115 Bonn, Germany.
Abouzied
Mekky M
MM
Gallitzendoerfer
Rainer
R
Gieselmann
Volkmar
V
Franken
Sebastian
S
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D019281:Dimerization; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D014404:Tubulin / Q000737:chemistry
D018797:Cell Cycle Proteins; C402392:Hdgfl3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014404:Tubulin