NSMF

The protein encoded by this gene is involved in guidance of olfactory axon projections and migration of luteinizing hormone-releasing hormone neurons. Defects in this gene are a cause of idiopathic hypogonadotropic hypogonadism (IHH). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

Full Name

NMDA Receptor Synaptonuclear Signaling And Neuronal Migration Factor

Function

Couples NMDA-sensitive glutamate receptor signaling to the nucleus and triggers long-lasting changes in the cytoarchitecture of dendrites and spine synapse processes. Part of the cAMP response element-binding protein (CREB) shut-off signaling pathway. Stimulates outgrowth of olfactory axons and migration of gonadotropin-releasing hormone (GnRH) and luteinizing-hormone-releasing hormone (LHRH) neuronal cells.

Biological Process

Cellular response to amino acid stimulusISS:UniProtKB
Cellular response to electrical stimulusISS:UniProtKB
Cellular response to gonadotropin stimulusISS:UniProtKB
Positive regulation of neuron migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of protein dephosphorylationISS:UniProtKB
Regulation of dendrite morphogenesisISS:UniProtKB
Regulation of neuron apoptotic processISS:UniProtKB
Regulation of neuronal synaptic plasticityISS:UniProtKB

Cellular Location

Nucleus
Nucleus envelope
Nucleus membrane
Nucleus matrix
Cytoplasm
Cytoplasm, cell cortex
Cytoplasm, cytoskeleton
Cell membrane
Cell projection, dendrite
Cell junction, synapse
Cell junction, synapse, synaptosome
Cell junction, synapse, postsynaptic density
Membrane
Found on the outside of the luteinizing-hormone-releasing hormone (LHRH) cell membrane and axons projecting from the olfactory pit and epithelium. Associates with transcriptionally active chromatin regions. Detected at the nuclear membranes of CA1 neurons. Cortical cytoskeleton. Localized in proximal apical dendrites. Colocalizes with CABP1 in dendrites and dendritic spines. Myristoylation is a prerequisite for extranuclear localization. Translocates from dendrites to the nucleus during NMDA receptor-dependent long-term potentiation (LTP) induction of synaptic transmission at Schaffer collateral/CA1 synapses of hippocampal primary neurons and in a importin-dependent manner (By similarity).

Involvement in disease

Hypogonadotropic hypogonadism 9 with or without anosmia (HH9):
A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).

PTM

Proteolytically processed after NMDA receptor activation. Cleaved in a calcium-dependent and calpain-sensitive manner. Calpain cleavage is essential for the translocation process from dendrites to the nucleus (By similarity).