What do we learn from the murineJacob/Nsmfgene knockout for human disease?
Mutations in the NSMF gene have been related to Kallmann syndrome. Conflicting results have been reported on the subcellular localization of Jacob/NELF, the protein encoded by the NSMF gene. Some reports indicate an extracellular localization and a function as a guidance molecule for migration of GnRH-positive neurons from the olfactory placode to the hypothalamus. Other studies have shown protein transport of Jacob from synapse-to-nucleus and indicate a role of the protein in neuronal activity-dependent gene expression. A recent publication casts doubts on a major role of Jacob/NELF in Kallmann syndrome and neuronal migration of GnRH-positive neurons during early development. Instead a murine NSMF gene knockout results in hippocampal dysplasia, impaired BDNF-signaling during dendritogenesis, and phenotypes related to the lack of BDNF-induced nuclear import of Jacob in early postnatal development.
RG Neuroplasticity, Leibniz-Institute for Neurobiology , Magdeburg, Germany.
Christina
C
Spilker
RG Neuroplasticity, Leibniz-Institute for Neurobiology , Magdeburg, Germany.
Katarzyna M
KM
Grochowska
RG Neuroplasticity, Leibniz-Institute for Neurobiology, Magdeburg, Germany; Leibniz Group "Dendritic Organelles and Synaptic Function", Hamburg, Germany.
Michael R
MR
Kreutz
BDNF; CREB; Jacob; Kallmann syndrome; NELF; hippocampus; synapse-to-nucleus