Eltahir, Heba Mahmoud Ahmed: Developmentally-regulated localization and possible functions of HRP-3 in the murine nervous tissue. - Bonn, 2010. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5N-21651
@phdthesis{handle:20.500.11811/4585,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5N-21651,
author = {{Heba Mahmoud Ahmed Eltahir}},
title = {Developmentally-regulated localization and possible functions of HRP-3 in the murine nervous tissue},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2010,
month = jun,

note = {HRP-3 is presented here as a hepatoma-derived growth factor family member that exhibits a unique expression pattern. Its expression is shown here to be restricted to the nervous system from the very early stages in the embryonic life until the adulthood. Interestingly, HRP-3 is restricted to neurons and shows a developmental stage-dependent expression pattern in cortical and sensory neurons both in vivo and in primary culture models prepared from both cell types in vitro. HRP-3 is expressed in the extranuclear compartment in embryonic nervous tissue and almost restricted to the nuclear compartment in the adult mouse nervous tissue.
The second part of this work focused on the possible intracellular and extracellular roles of HRP-3. It was possible to prove that the intracellular level of HRP-3 plays an important role in promoting neurite outgrowth and neuronal cell sprouting. Reducing the intracellular level of HRP-3 in one of the primary cell culture models using synthetic siRNAs against HRP-3 resulted in negative effects on neuronal cell differentiation. This effect was reversed by over-expressing HRP-3 within an inducible neuronal cell model. The nuclear localising signal located in the carboxy terminus (NLS2) of HRP-3 is the one responsible for its nuclear localisation while the nuclear localising signal located in its amino terminus (NLS1) is the one responsible for its neurite outgrowth promoting effect. These effects of HRP-3 are mediated through its interaction with microtubules as shown in studies based partially on this work.
The results also show that extracellular HRP-3 has a positive effect on the differentiation of primary cortical neurons. It is also released by cortical neurons themselves to promote their own survival and differentiation and can protect primary cortical neurons cultured in stressful, supplement-free conditions.
Together, the results point to interesting roles of HRP-3 during the development of the nervous system. This work can be the basis for further interesting studies that may include an explanation of the molecular mechanisms through which it exerts its roles, like detecting the receptor through which HRP-3 signals and the signalling transduction pathways that result in these effects.},

url = {https://hdl.handle.net/20.500.11811/4585}
}

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