In human importin [alpha], for example, there exists an [alpha]1 subfamily (importin [alpha]5 (KPNA1), [alpha]6 (KPNA5), and [alpha]7 (KPNA6)), [alpha]2 subfamily (importin [alpha]1 (KPNA2) and [alpha]8 (KPNA7)), and [alpha]3 subfamily (importin [alpha]3 (KPNA4) and [alpha]4 (KPNA3)) (Fig.
For example, the expression patterns of importin [alpha] subtypes were shown to change during cell differentiation processes, and, more importantly, its modulation clearly affects cell differentiation processes such as the differentiation of embryonic stem cells into neural cells (KPNA1 (73)), myoblasts into myotubes (KPNA2 (77)), or maturation of oligodendrocyte progenitors (KPNA1, (80) KPNA4 (78)).
Intriguingly, a comparison of KPNA1, KPNA4, and KPNA6 knockout mice revealed that KPNA6 knockout mice are highly resistant to infection with influenza viruses, (87) highlighting the importance of importin [alpha] as a determinant of pathogenicity.
Several proteins were differentially expressed, which included karyopherin alpha 4 (KPNA4
) overexpressed only in paralytic rabies, calcium calmodulin dependent kinase 2 alpha (CAMK2A) which was upregulated in paralytic rabies, and glutamate ammonia ligase (GLUL) which was overexpressed both in paralytic and encephalitic rabies.