RGD Reference Report - Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein. - Rat Genome Database

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Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein.

Authors: Kurschner, C  Yuzaki, M 
Citation: Kurschner C and Yuzaki M, J Neurosci. 1999 Sep 15;19(18):7770-80.
RGD ID: 11041033
Pubmed: PMID:10479680   (View Abstract at PubMed)
PMCID: PMC6782450   (View Article at PubMed Central)

Interleukin (IL)-16 is a proinflammatory cytokine that has attracted widespread attention because of its ability to block HIV replication. We describe the identification and characterization of a large neuronal IL-16 precursor, NIL-16. The N-terminal half of NIL-16 constitutes a novel PDZ domain protein sequence, whereas the C terminus is identical with splenocyte-derived mouse pro-IL-16. IL-16 has been characterized only in the immune system, and the identification of NIL-16 marks a previously unsuspected connection between the immune and the nervous systems. NIL-16 is a cytosolic protein that is detected only in neurons of the cerebellum and the hippocampus. The N-terminal portion of NIL-16 interacts selectively with a variety of neuronal ion channels, which is similar to the function of many other PDZ domain proteins that serve as intracellular scaffolding proteins. Among the NIL-16-interacting proteins is the class C alpha1 subunit of a mouse brain calcium channel (mbC alpha1). The C terminus of NIL-16 can be processed by caspase-3, resulting in the release of secreted IL-16. Furthermore, in cultured cerebellar granule neurons undergoing apoptosis, NIL-16 proteolysis parallels caspase-3 activation. Cerebellar granule neurons express the IL-16 receptor CD4. Exposure of these cells to IL-16 induces expression of the immediate-early gene, c-fos, via a signaling pathway that involves tyrosine phosphorylation. This suggests that IL-16 provides an autocrine function in the brain. Therefore, we hypothesize that NIL-16 is a dual function protein in the nervous system that serves as a secreted signaling molecule as well as a scaffolding protein.

Objects referenced in this article
Gene Grin2d glutamate ionotropic receptor NMDA type subunit 2D Rattus norvegicus
Gene Kcnj10 potassium inwardly-rectifying channel, subfamily J, member 10 Rattus norvegicus

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