KIBRA: In the brain and beyond

Abstract

In mammals, the KIBRA locus has been associated with memory performance and cognition by genome-wide single nucleotide polymorphism screening. Genetic studies in Drosophila and human cells have identified KIBRA as a novel regulator of the Hippo signaling pathway, which plays a critical role in human tumorigenesis. Recent studies also indicated that KIBRA is involved in other physiological processes including cell polarity, membrane/vesicular trafficking, mitosis and cell migration. At the biochemical level, KIBRA protein is highly phosphorylated by various kinases in epithelial cells. Here, we discuss the updates concerning the function and regulation of KIBRA in the brain and beyond.

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

“…The mechanism/s by which these two polymorphisms (KIBRA rs17070145, CLSTN2 rs6439886) may influence episodic memory functioning is unclear. KIBRA encodes a phosphoprotein, which binds to many proteins including those implicated in neuronal and synaptic plasticity, cell migration, vesicular transport, mitosis and tumorigenesis (Zhang et al, 2014). It has been proposed that KIBRA regulates AMPA receptors, the major excitatory synaptic receptors of the brain, suggesting KIBRA may be involved in synaptic plasticity and transmission (Makuch et al, 2011;Zhang et al, 2014).…”

“…Both KIBRA and CLSTN2 are highly expressed in the medial temporal lobe (Zhang et al, 2014;Schneider et al, 2010;Hintsch et al, 2002), a brain region important for episodic memory (Squire, Stark, & Clark, 2004). Moreover, it has been shown that in the Older Australian Twins Study and other cohorts that ~53-65 % of the variance in hippocampal volume can be attributed to genetic influences (Blokland, de Zubicaray, McMahon, & Wright, 2012;Mather et al, 2015).…”

“…KIBRA encodes a phosphoprotein, which binds to many proteins including those implicated in neuronal and synaptic plasticity, cell migration, vesicular transport, mitosis and tumorigenesis (Zhang et al, 2014). It has been proposed that KIBRA regulates AMPA receptors, the major excitatory synaptic receptors of the brain, suggesting KIBRA may be involved in synaptic plasticity and transmission (Makuch et al, 2011;Zhang et al, 2014). CLSTN2 is part of the components of the postsynaptic membrane and is located predominately in excitatory synapses giving CLSTN2 a role in intracellular postsynaptic signaling, potentially mediating specific responses in excitatory synaptic transmission (Hintsch et al, 2002).…”

Phosphorylation-Dependent Regulation of the DNA Damage Response of Adaptor Protein KIBRA in Cancer Cells

“…Later, it was reported that KIBRA interacts with discoidin domain receptor 1 and modulates collagen-induced extracellular signal-regulated kinase (ERK) signaling in normal breast cells (13). KIBRA also functions as an adaptor protein that exercises its functions by interacting with other proteins (14).…”

Response to: Further Support for an Association between the Memory-Related Gene WWC1 and Posttraumatic Stress Disorder: Results from the Detroit Neighborhood Health Study

“…By contrast, rs10038727, the SNP found to be associated with PTSD (6,7), is located much closer to the regions encoding the PKMζ interaction site. Zhang et al (11) highlighted the existence of an exonic mutation at this site, which most likely influences PKMζ binding affinity (11) and only maps approximately 1000 base pairs from rs10038727. On the other hand, rs10038727, despite being an intronic variant, could be functional itself by altering transcription factor binding sensitivity (6).…”