Localization of the Extracellular Matrix Protein SC1 Coincides with Synaptogenesis During Rat Postnatal Development

Lively, Starlee; Brown, Ian R.

doi:10.1007/s11064-008-9606-z

Cited by 21 publications

(25 citation statements)

References 28 publications

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“…The major reason for our interest in two specific post-natal stages was that P6 and P15 were two crucial points in hippocampal development when GABAergic signaling switched from excitatory to inhibitory, and synaptogenesis attained its peak, respectively [20,35]. The PKC isozymes PKCε and PKCα appeared to be differentially involved during early post-natal development of the hippocampus [23].…”

Section: Resultsmentioning

confidence: 99%

Regulation of protein kinase C isozymes during early postnatal hippocampal development

et al. 2009

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During neonatal hippocampal development, serotonin 1A receptor-mediated signaling initially employs PKCε to boost neuronal proliferation and then uses PKCα to promote synaptogenesis. Such stage-specific involvement of a PKC isozyme could be determined by its relative expression level. In mouse hippocampi, we detected relatively low levels of α, β, γ, and δ isozymes at post-natal days 2–6 (P2–6), which was followed by a large increase in their expression. In contrast, the PKC isozymes ε and θ were relatively abundant at P6, following which they underwent a further increase by P15. Comparison with purified proteins confirmed that the PKCε levels at P6 and P15 were respectively 1.75 and 7.36 ng per 60 µg of protein, whereas PKCα levels at P6 and P15 were respectively 160 pg and 1.186 ng per 60 µg of protein. Therefore, at P6, PKCepsilon was about 11-fold more abundant than PKCα. Consequently, signaling cascades could use the relatively abundant PKCε (and possibly PKCθ) molecules for early events at P2-6 (e.g. neurogenesis), following which PKCα (and the β, γ, or δ isozymes) could guide maturation or apoptosis. Notably, at P6 but not P15, PKCε, was localized to the nuclei of neuroblasts, probably directing mitosis. In contrast, at P15 but not P6, PKCα was highly expressed in the processes of the differentiated hippocampal neurons. In summary, PKC isozymes follow differential profiles of expression in neonatal hippocampus and the relative abundance of each may determine its mode and stage of involvement in hippocampal development.

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Section: Resultsmentioning

confidence: 99%

Regulation of protein kinase C isozymes during early postnatal hippocampal development

et al. 2009

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“…We have also demonstrated that SC1 is associated with the formation of synapses in the cerebellum during postnatal development [22]. These findings suggest that SC1 plays a role at the synapse in the cerebellum; however, the manner in which SC1 protein reaches perisynaptic processes remains to be identified.…”

Section: Introductionmentioning

confidence: 64%

“…Colocalization of SC1 with synaptophysin and its presence at synapses in the molecular layer suggest that SC1 may be involved in remodeling processes that occur at the synapse both during development and in the adult cerebellum. SC1 does not localize to neurons in the cerebellum [22]. Consequently, SC1 at synapses in the molecular layer likely originates from Bergmann glial cells.…”

Section: Discussionmentioning

confidence: 91%

“…However, continued expression of SC1 protein along Bergmann glial fibers after the completion of granule cell migration suggests that SC1 possesses additional roles in the cerebellum that extend beyond cell migration. We have recently shown that localization of SC1 protein in the cerebellum coincides with synaptophysin during postnatal development suggesting a role for SC1 in synaptogenesis [22]. In addition, we have previously demonstrated that SC1 localizes to perisynaptic glial processes that envelope synapses in the molecular layer in the adult cerebellum [21].…”

Section: Discussionmentioning

confidence: 98%

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The Extracellular Matrix Protein SC1/Hevin Localizes to Multivesicular Bodies in Bergmann Glial Fibers in the Adult Rat Cerebellum

Lively

Brown

2009

Neurochem Res

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SC1 is an extracellular matrix molecule prominent in the mammalian brain. In the cerebellum, SC1 localizes to Bergmann glial cells and perisynaptic glial processes that envelop synapses in the molecular layer. In the present study, confocal microscopy revealed a punctate distribution of SC1 along Bergmann glial fibers that colocalized with the intermediate filament GFAP when fibers were viewed in cross-section. Immunoelectron microscopy showed that the punctate SC1 pattern corresponded to the localization of SC1 in multivesicular bodies situated within Bergmann glial fibers. The pattern of SC1 localization was not disrupted following hyperthermia or pilocarpine-induced status epilepticus. The present study suggests that SC1 protein may reach its destination in perisynaptic glial processes and glial endfeet by transport along Bergmann glial fibers in multivesicular bodies and that this process is preserved following stress.

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“…During the first few weeks of postnatal development, SPARC and Hevin are highly expressed in astrocytes [9, 31], with Hevin also being present in neurons [36]. Secretion of SPARC and Hevin from astrocytes has been shown to play an important role during synapse development (recently reviewed in [5, 11]).…”

Section: Sparc and Hevin/sc1mentioning

confidence: 99%

Astrocyte-Secreted Matricellular Proteins in CNS Remodelling during Development and Disease

2014

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Matricellular proteins are secreted, nonstructural proteins that regulate the extracellular matrix (ECM) and interactions between cells through modulation of growth factor signaling, cell adhesion, migration, and proliferation. Despite being well described in the context of nonneuronal tissues, recent studies have revealed that these molecules may also play instrumental roles in central nervous system (CNS) development and diseases. In this minireview, we discuss the matricellular protein families SPARC (secreted protein acidic and rich in cysteine), Hevin/SC1 (SPARC-like 1), TN-C (Tenascin C), TSP (Thrombospondin), and CCN (CYR61/CTGF/NOV), which are secreted by astrocytes during development. These proteins exhibit a reduced expression in adult CNS but are upregulated in reactive astrocytes following injury or disease, where they are well placed to modulate the repair processes such as tissue remodeling, axon regeneration, glial scar formation, angiogenesis, and rewiring of neural circuitry. Conversely, their reexpression in reactive astrocytes may also lead to detrimental effects and promote the progression of neurodegenerative diseases.

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Localization of the Extracellular Matrix Protein SC1 Coincides with Synaptogenesis During Rat Postnatal Development

Cited by 21 publications

References 28 publications

Regulation of protein kinase C isozymes during early postnatal hippocampal development

Regulation of protein kinase C isozymes during early postnatal hippocampal development

The Extracellular Matrix Protein SC1/Hevin Localizes to Multivesicular Bodies in Bergmann Glial Fibers in the Adult Rat Cerebellum

Astrocyte-Secreted Matricellular Proteins in CNS Remodelling during Development and Disease

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