QKI Antibody Review

 

 

 

Introduction

  • an RNA-binding protein belonging to a growing protein family called STAR (signal transduction and activator of RNA), and essential for myelination in the central nervous system (CNS). PMID: 10506177, PMID: 12682013

  • a new candidate gene for schizophrenia involved in myelination. PMID: 16342280, PMID: 16641098

  • QKI levels may regulate oligodendrocyte differentiation and maturation in human brain, in a similar way as in mouse. PMID: 16641098

  • involved in glial cell differentiation in mice. PMID: 14706070

  • quaking proteins (QKI-5, QKI-6, and QKI-7) are essential for embryogenesis and myelination. PMID: 10535969

  • play key roles in controlling the homeostasis of their mRNA targets. PMID: 17079655

Normal Expression

  • QKI proteins are expressed by differentiated glia and have been implicated as regulators of myelination, but are also thought to function during early neural development. PMID: 9778149

  • Using X-gal and immunohistochemical staining, qkI is first shown to be expressed in endothelial cells and smooth muscle cells. PMID: 14706070

  • We show that in mature oligodendrocytes in culture, the localization of cytoplasmic QKI isoforms requires an intact cytoskeleton. PMID: 11178867

  • Three QKI isoforms have different carboxyl termini and different subcellular localization. Here, using GFP fusion protein, we identified a 7-amino acid novel nuclear localization sequence in the carboxyl terminus of QKI-5, which is conserved in a subclass of STAR proteins containing SAM68 and ETLE/T-STAR. PMID: 10506177

  • Although the qkI messages and their products are abundant in brain and heart, a lower level of expression was found in various other tissues tested. PMID: 10384037

  • QKI proteins are expressed in neural progenitors of the ventricular zone (vz) during murine CNS development, but that their expression is down-regulated during neuronal differentiation. By contrast, neural progenitors located in specific subdomains of the vz maintain expression of QKI proteins as they differentiate and migrate away into the emerging nervous system. These QKI+ cells have characteristics consistent with the acquisition of a glial rather than neuronal fate. PMID: 9778149

  • Antibodies raised to the unique carboxy peptides of the resulting QKI proteins reveal that, in the nervous system, all three QKI proteins are expressed strongly in myelin-forming cells and also in astrocytes. Interestingly, individual isoforms show distinct intracellular distributions: QKI-6 and QKI-7 are localized to perikaryal cytoplasm, whereas QKI-5 invariably is restricted to the nucleus, consistent with the predicted role of QKI as an RNA-binding protein. In quakingviable mutants, which display severe dysmyelination, QKI-6 and QKI-7 are absent exclusively from myelin-forming cells. By contrast, QKI-5 is absent only in oligodendrocytes of severely affected tracts. PMID: 8987822

Expression Alteration

  • transition from premyelinating oligodendrocytes into myelin-bearing cells is accompanied by a dramatic upregulation in expression of the RNA binding QKI proteins. PMID: 11178867

  • In vitro, neural progenitor cells also down-regulate QKI expression as they differentiate into neurons, but not if they differentiate into glia. PMID: 9778149

Function

  • QKI protein has a critical regulatory role in smooth muscle cell development. PMID: 14706070

  • using an interspecies heterokaryon assay, we found that QKI-5, but not another STAR protein ETLE, shuttles between the nucleus and the cytoplasm, which suggests that QKI-5 functions in both cell compartments. PMID: 10506177

  • QKI is absent in neurons, QKI-dependent stabilization of MAP1B mRNA provides a novel mechanism for advancing MAP1B expression specifically in oligodendroglia during brain development. PMID: 16855020

  • QKI-6 is the major isoform responsible for CNS myelination, which preferentially promotes MBP expression in oligodendrocytes. PPMID: 17079655

Applications

 

Immunohistochemistry (IHC)

  • Using X-gal and mmunohistochemical staining, qkI is first shown to be expressed in endothelial cells and smooth muscle cells. PMID: 14706070

  • IIn the qk(v)/qk(v) brain, immunostaining of QKI proteins is diminished in an isoform-differential manner with undefined mechanisms. We examined the expression of QKI protein isoforms and qkI mRNA isoforms in the qk(v)/qk(v) mutants and the non-phenotypic wt/qk(v) littermates. PMID: 12888522