Regional Distribution and Cell Type-Specific Subcellular Localization of Prothymosin Alpha in Brain

Abstract

Prothymosin alpha (ProTα) is an acidic nuclear protein implicated in several cellular functions including cell survival. ProTα is found in the central nervous system, but the regional and cell type-specific expression patterns are not known. In this study, our immunohistochemical analysis demonstrated that ProTα is expressed ubiquitously throughout adult brain with difference in the intensity of region-specific protein reactivity. Interestingly, the highest ProTα signals were observed in the brain regions relevant to neurogenesis, such as sub-ventricular zone, granular cell layer of dentate gyrus, as well as granule cell layer of olfactory bulb. Strong immunoreactivity was also found in habenula, ependymal cells lining the dorsal third and fourth ventricle, and in neurons in the Purkinje cell layer of cerebellum. We showed that ProTα was strictly localized in the nuclei of neurons, while it was found in the cytosolic space of astroglial and microglial processes and cell body in the adult brain. To clarify the phenomenon underlying cytosolic localization of ProTα in non-neuronal cells, ZVAD-fmk, a caspase-3 inhibitor, was delivered intracerebroventricularly in the brain. At the follow-up 24 h after ZVAD-fmk injection, we found that nuclear intensity of ProTα was significantly increased in astrocytes, whereas the ProTα expression was not affected in microglia. The present study would contribute toward better understanding of physiological and pathophysiological roles of ProTα in the brain.

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“…Secretion of C3 in ADEV‐IL‐1β therefore appears to be a mechanism by which inflammatory signals are propagated. PTMA is a highly acidic protein, that is, expressed both in the nucleus and cytosol of astrocytes (Halder & Ueda, ). Similar to C3, PTMA is also involved in propagation of inflammatory signals via its C‐terminal domain that stimulates pro‐inflammatory responses and cytokine expression through activation of toll like receptor 4 (Gusella, Teixeira, Aberg, Uversky, & Mosoian, ; Ioannou et al, ; Mosoian et al, ).…”

Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

“…This enzyme regulates the brain levels of homocysteine, an excitatory amino acid, protecting hippocampal neurons against oxidative stress [ 122 , 123 ]. Two VIPs are also involved in responses to stress: RPL6 whose gene product is ribosomal protein L6, a regulator of the HDM2 —p53 pathway in response to ribosomal stress [ 124 ]; and DTWD2 , coding for prothymosin alpha, a highly acidic nuclear protein of the alpha-thymosin family involved in response to oxidative stress and neuronal survival [ 125 ]. Finally, two hubs, C6orf25 and PNPLA7 , are also related to protective roles.…”

Prothymosin alpha‐deficiency enhances anxiety‐like behaviors and impairs learning/memory functions and neurogenesis

“…; Cameron and Glover ). Since strong ProTα signals were detected in the SGZ of the hippocampal DG (Halder and Ueda ), we hypothesize that ProTα has crucial roles in the regulation of anxiety‐related behaviors, learning/memory‐functions, and neurogenesis. In this study, we have generated and used ProTα knockout mice to test this hypothesis.…”

“…However, characterizing the physiological roles of endogenous ProTα in the brain without stress remains elusive. We previously demonstrated that ProTα protein is ubiquitously expressed throughout the adult mouse brain (Halder and Ueda ). Moreover, strong ProTα signals were detected in the neuronal cells in some brain regions, specifically in the adult neurogenesis‐related areas including the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus, the subventricular zone, and the olfactory bulb (Olf), proposing the idea that ProTα is involved in adult neurogenesis (Halder and Ueda ).…”

“…We previously demonstrated that ProTα protein is ubiquitously expressed throughout the adult mouse brain (Halder and Ueda ). Moreover, strong ProTα signals were detected in the neuronal cells in some brain regions, specifically in the adult neurogenesis‐related areas including the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus, the subventricular zone, and the olfactory bulb (Olf), proposing the idea that ProTα is involved in adult neurogenesis (Halder and Ueda ). It is well‐known that adult hippocampal neurogenesis plays crucial roles in the regulation of affective states including fear/anxiety, learning/memory, and synaptic plasticity (Revest et al .…”