Visinin-like Protein (VILIP) Is a Neuron-specific Calcium-dependent Double-stranded RNA-binding Protein

Abstract

Double-stranded RNA-binding proteins function in regulating the stability, translation, and localization of specific mRNAs. In this study, we have demonstrated that the neuron-specific, calcium-binding protein, visinin-like protein (VILIP) contains one double-stranded RNA-binding domain, a protein motif conserved among many double-stranded RNA-binding proteins. We showed that VILIP can specifically bind doublestranded RNA, and this interaction specifically requires the presence of calcium. Mobility shift studies indicated that VILIP binds double-stranded RNA as a single protein-RNA complex with an apparent equilibrium dissociation constant of 9.0 ؋ 10 ؊6 M. To our knowledge, VILIP is the first double-stranded RNA-binding protein shown to be calcium-dependent. Furthermore, VILIP specifically binds the 3-untranslated region of the neurotrophin receptor, trkB, an mRNA localized to hippocampal dendrites in an activity-dependent manner. Given that VILIP is also expressed in the hippocampus, these data suggest that VILIP may employ a novel, calcium-dependent mechanism to regulate its binding to important localized mRNAs in the central nervous system.

Identification of Process-Localized mRNAs from Cultured Rodent Hippocampal Neurons

“…Tpt1 (translationally controlled tumor protein 1) binds EF1␣ in the GDP-bound configuration (Cans et al, 2003), thereby increasing translational efficiency. Visinin-like protein-1 has been shown by Mathisen et al (1999) to bind double-stranded RNA, specifically the 3Ј-untranslated region of tyrosine receptor kinase B mRNA, which is also dendritically localized, in a calcium-dependent manner (Tongiorgi et al, 1997). In Drosophila oocytes, the hnRNP A/B homolog, Hrp48, has been shown to bind the 5Ј-and 3Ј-untranslated regions of oskar mRNA and repress its translation during transport (Huynh et al, 2004;Yano et al, 2004).…”

Molecular cloning and expression of visinin-like protein 1 from Gekko japonicus spinal cord

“…3; EF-hand 1-4). The other functional VILIP dsRNAbinding domain described by Mathisen et al (1999) is located at L 110 -V 182 . It thus appears that gecko VILIP-1 can also regulate its binding to important localized mRNAs in the central nervous system.…”

“…In comparison with many biological functions reported in the neurons, very little Gecko visinin-like protein 1 165 information is available regarding physiological roles in other tissues. In neurons of the central nervous system, VILIP-1 can specifically bind the 3'-untranslated region (3'UTR) of the neurotrophin receptor TrkB in a Ca 2+ -dependent manner (Mathisen et al 1999). TrkB is found to be activated in the injured spinal cord and implicates a role in spinal cord regeneration (Frisén et al 1992;Liebl et al 2001;Widenfalk et al 2001).…”

Visinin-like protein 1 regulates natriuretic peptide receptor B in the heart

“…VILIP-1 is expressed at high levels in the brain and its role in the central nervous system has been addressed in a number of studies [6,[11][12][13]. Expression of VILIP-1 was also reported for the heart, pancreas, reproductive organs, and colon, however, its function in extra-neuronal tissues is still poorly understood [14].…”

“…VILIP-1 modulates clathrin-dependent receptor cycling in the central nervous system supporting its general role in membrane trafficking [9]. VILIP-1 has also been shown to regulate gene expression by formation of protein-RNA-complexes that modulate localization and stability of specific mRNAs and possibly by affecting the cAMP/CREB pathway [8,11].…”