Plasticity-related gene 3 promotes neurite shaft protrusion
Recently, we and others proposed plasticity-related gene 3 (PRG3) as a novel molecule in neuritogenesis based on PRG3 overexpression experiments in neuronal and non-neuronal cell lines. However, direct information on PRG3 effects in neuronal development and, in particular, its putative spatio-temporal distribution and conditions of action, is sparse.
We demonstrate here that PRG3 induces filopodia formation in HEK293 cells depending on its N-glycosylation status. The PRG3 protein was strongly expressed during mouse brain development in vivo from embryonic day 16 to postnatal day 5 (E16 – P5). From P5 on, expression declined. Furthermore, in early, not yet polarized hippocampal cultured neurons, PRG3 was expressed along the neurite shaft. Knock-down of PRG3 in these neurons led to a decreased number of neurites. This phenotype is rescued by expression of an shRNA-resistant PRG3 construct in PRG3 knock-down neurons. After polarization, endogenous PRG3 expression shifted mainly to axons, specifically to the plasma membrane along the neurite shaft. These PRG3 pattern changes appeared temporally and spatially related to ongoing synaptogenesis. Therefore we tested (i) whether dendritic PRG3 re-enhancement influences synaptic currents and (ii) whether synaptic inputs contribute to the PRG3 shift. Our results rendered both scenarios unlikely: (i) PRG3 over-expression had no influence on miniature excitatory postsynaptic currents (mEPSC) and (ii) blocking of incoming signals did not alter PRG3 distribution dynamics. In addition, PRG3 levels did not interfere with intrinsic neuronal properties.
Taken together, our data indicate that endogenous PRG3 promotes neurite shaft protrusion and therefore contributes to regulating filopodia formation in immature neurons. PRG3 expression in more mature neurons, however, is predominantly localized in the axon. Changes in PRG3 levels did not influence intrinsic or synaptic neuronal properties.
- Plasticity-related gene 3 promotes neurite shaft protrusion
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
- Online Date
- March 2013
- Online ISSN
- BioMed Central
- Additional Links
- Cell differentiation
- Growth cone
- Author Affiliations
- 3. Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité – Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany
- 1. Netherlands Institute for Neuroscience, Meibergdreef 47, Amsterdam, 1105, BA, The Netherlands
- 2. Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel, CH 4058, Switzerland