Sensorimotor enhancement in mouse mutants lacking the Purkinje cell-specific Gi/o modulator, Pcp2(L7)

Iscru, Emilia; Serinagaoglu, Yelda; Schilling, Karl; Tian, Jin Bin; Bowers-Kidder, Stephanie L.; Zhang, Rui; Morgan, James I.; DeVries, A. Courtney; Nelson, Randy J.; Zhu, Michael X.; Oberdick, John

doi:10.1016/j.mcn.2008.09.002

Cited by 24 publications

(45 citation statements)

References 79 publications

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“…ProTa-related transgenic mice. Most interestingly, stronger ProTa signals that were found in neurons in Purkinje cell layer of cerebellum play an important role in movement, posture, and cognitive functions (Jorntell and Hansel 2006;Iscru et al 2009). In this study we successfully demonstrated the cell type-specific sub-cellular localization of ProTa in adult brain.…”

Section: Discussionmentioning

confidence: 99%

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

Halder

Ueda

2011

Cell Mol Neurobiol

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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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Section: Discussionmentioning

confidence: 99%

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

Halder

Ueda

2011

Cell Mol Neurobiol

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“…Some of these molecules display highly restricted and complex parasagittal patterns. Examples are aldolase C/zebrin II [46], gene transcription factors [41,47], intracellular signaling molecules (CaBP, cGK [48]; Pcp2/L7 [49][50][51]); ephrins, and Eph receptors [47,52]; and members of the cadherin superfamily (see below).…”

Section: Cadherins At Intermediate Stages Of Cerebellar Cortical Devementioning

confidence: 99%

Cadherins in Cerebellar Development: Translation of Embryonic Patterning into Mature Functional Compartmentalization

2010

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Cadherins are cell adhesion molecules with multiple morphogenic functions in brain development, for example, in neuroblast migration and aggregation, axon navigation, neural circuit formation, and synaptogenesis. More than 100 members of the cadherin superfamily are expressed in the developing and mature brain. Most of the cadherins investigated, in particular classic cadherins and δ-protocadherins, are expressed in the cerebellum. For several cadherin subtypes, expression begins at early embryonic stages and persists until mature stages of cerebellar development. At intermediate stages, distinct Purkinje cell clusters exhibit unique rostrocaudal and mediolateral expression profiles for each cadherin. In the chicken, mouse, and other species, the Purkinje cell clusters are separated by intervening raphes of migrating granule cells. This pattern of Purkinje cell clusters/raphes is, at least in part, continuous with the parasagittal striping pattern that is apparent in the mature cerebellar cortex, for example, for zebrin II/aldolase C. Moreover, subregions of the deep cerebellar nuclei, vestibular nuclei and the olivary complex also express cadherins differentially. Neuroanatomical evidence suggests that the nuclear subregions and cortical domains that express the same cadherin subtype are connected to each other, to form neural subcircuits of the cerebellar system. Cadherins thus provide a molecular code that specifies not only embryonic structures but also functional cerebellar compartmentalization. By following the implementation of this code, it can be revealed how mature functional architecture emerges from embryonic patterning during cerebellar development. Dysfunction of some cadherins is associated with psychiatric diseases and developmental impairments and may also affect cerebellar function.

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“…On the other hand, it may be that Pcp2 is important for certain currently unidentified roles. Indeed, some evidence of this has already been reported (Xu et al, 2008;Iscru et al, 2009).…”

Section: Discussionmentioning

confidence: 69%

“…Detailed behavioral studies showed these mutants to possess enhanced motor learning abilities (Iscru et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Expression of a novel splicing variant of Pcp2 in closely related laboratory rodents

Przybyła

Nowacka-Chmielewska²,

Barski

2016

Genet. Mol. Res.

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ABSTRACT. Purkinje cell protein-2 (PCP2), also known as L7, is a member of the GoLoco protein family with highly cell-specific expression, being restricted to cerebellar Purkinje cells and retinal bipolar neurons in various species. However, its function in these tissues is unknown. Previous studies have suggested that PCP2 is a guanine nucleotide dissociation inhibitor, or a guanine nucleotide exchange factor. The Pcp2 gene is known to have many splice variants in both cerebellar Purkinje cells and retinal bipolar neurons. Here, we tested the hypothesis that a novel Pcp2 splice variant is conserved in closely related laboratory rodents (mice, rats, and hamsters). After analyzing alternative splicing of this gene in the Purkinje cells and retinas of these rodent species, we confirmed the presence of the novel longer transcript in mice. However, assessment of Pcp2 transcripts using polymerase chain reaction amplification of complementary DNA revealed this long splice variant containing the additional exon 3B to be absent from rats and hamsters. Thus, the novel Pcp2 transcript is particular to mouse cerebellar Purkinje cells and retinal bipolar neurons. It is likely to have arisen in this species, as a result of spontaneous mutation or de novo rearrangements. This gene presumably serves a very specific and, as yet, unknown function in the eyes and/or Purkinje cells of mice.

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Sensorimotor enhancement in mouse mutants lacking the Purkinje cell-specific Gi/o modulator, Pcp2(L7)

Cited by 24 publications

References 79 publications

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

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

Cadherins in Cerebellar Development: Translation of Embryonic Patterning into Mature Functional Compartmentalization

Expression of a novel splicing variant of Pcp2 in closely related laboratory rodents

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