NMDA receptor synaptonuclear signaling & neuronal migration factor; nasal embryonic luteinizing hormone-releasing hormone factor; nasal embryonic LHRH factor (NSMF NELF)
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Function
- couples NMDA-sensitive glutamate receptor signaling to the nucleus & triggers long-lasting changes in the cytoarchitecture of dendrites & spine synapse processes
- part of the cAMP response element-binding protein (CREB) shut-off signaling pathway
- stimulates outgrowth of olfactory axons & migration of GnRH & LHRH neuronal cells
- proteolytically processed after NMDA receptor activation
- cleaved in a Ca+2-dependent & calpain-sensitive manner
- calpain cleavage is essential for the translocation from dendrites to the nucleus (putative)
- interacts with KPNA1
- interaction occurs in a Ca+2-independent manner after synaptic NMDA receptor stimulation & is required for nuclear import of NSMF but is competively inhibited by CABP1
- interacts (via the central NLS-containing motif region) with CABP1 (via EF-hands 1 & 2)
- interaction occurs in a Ca+2-dependent manner after synaptic NMDA receptor stimulation & prevents the nuclear import of NSMF
- no competitive inhibition by calmodulin (putative)
- role in outgrowth of olfactory axons
- role in migration of LHRH neurons
Structure
belongs to the NSMF family
Compartment
- cell membrane, nucleus, nuclear envolope
- cytoplasm, cytoskeleton
- cell projection, dendrite
- cell junction, synapse, synaptosome, post-synaptic density
- found on the outside of the LHRH cell membrane & axons projecting from the olfactory pit & epithelium
- associates with transcriptionally active chromatin regions
- detected at the nuclear membranes of CA1 neurons
- localized in proximal apical dendrites
- colocalizes with CABP1 in dendrites & dendritic spines.
- myristoylation is a prerequisite for extranuclear localization
- translocates from dendrites to the nucleus during at Schaffer collateral/CA1 synapses (importin-dependent)
- NSMF mRNA expressed in the hippocampus exhibits a prominent dendritic localization which is mediated by a dendritic targeting element (DTE) residing in the 3'-untranslated region (3'UTR)
- transport from dendrites to the nucleus is induced by NMDA receptor activation & results in a rapid stripping of synaptic contacts & a reduction of dendritic complexity
Alternative splicing
named isoforms=5
Expression
- highly expressed in adult & fetal brain
- weakly expressed in heart, liver, spleen, testis, small intestine, skeletal muscle, peripheral blood leukocytes & kidney
Pathology
- defects in NELF may be associated with hypogonadotropic hypogonadism