Activity and localization of the Secretory Pathway Ca2+-ATPase isoform 1 (SPCA1) in different areas of the mouse brain during postnatal development

Sepúlveda, M. Rosario; Marcos, Daniel; Berrocal, María Cruz; Raeymaekers, Luc; Mata, Ana M.; Wuytack, Frank

doi:10.1016/j.mcn.2008.02.012

Cited by 29 publications

(47 citation statements)

References 34 publications

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“…These results are comparable to those found in adult tissue (Fig. 5C) and also to those described in postnatal developing mouse hippocampal tissue (Sepú lveda et al, 2008).…”

Section: Suppression Of Spca1 In Mouse Hippocampal Neurons Also Impaisupporting

confidence: 91%

“…The SPCA1 distribution shifts from one corresponding to a single-copy juxtanuclear Golgi position to multiple complexes distributed over the neural soma, with a clear preference for dendritic positioning in stages of rapid dendritic outgrowth (Horton and Ehlers, 2003). This in vitro pattern is similar to that observed in mouse developing brain (Sepú lveda et al, 2008). In fact, it has been recently reported that growth of neuronal dendrites is more dependent on the classical secretory pathway than axon growth, a property that is probably related to the position of the somatic Golgi toward the dendrites (Horton and Ehlers, 2003;Ye et al, 2007).…”

Section: Discussionsupporting

confidence: 61%

“…SPCAs also play a key task in Mn 2ϩ homeostasis, since they are the only known P-type ATPases that can transport Mn 2ϩ with high affinity (Van Baelen et al, 2001;Ton et al, 2002). In a previous work, we have shown the presence of SPCA1 in the soma and in the proximal part of dendritic trunks of main brain neurons from the earliest postnatal stages on (Sepú lveda et al, 2008). However, the contribution of SPCA1 to these developmental processes remained unknown.…”

Section: Introductionmentioning

confidence: 94%

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Silencing the SPCA1 (Secretory Pathway Ca²⁺-ATPase Isoform 1) Impairs Ca²⁺Homeostasis in the Golgi and Disturbs Neural Polarity

Sepúlveda¹,

Vanoevelen²,

Raeymaekers³

et al. 2009

J. Neurosci.

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Neural cell differentiation involves a complex regulatory signal transduction network in which Ca2ϩ ions and the secretory pathway play pivotal roles. The secretory pathway Ca 2ϩ -ATPase isoform 1 (SPCA1) is found in the Golgi apparatus where it is actively involved in the transport of Ca 2ϩ or Mn 2ϩ from the cytosol to the Golgi lumen. Its expression during brain development in different types of neurons has been documented recently, which raises the possibility that SPCA1 contributes to neuronal differentiation. In the present study, we investigated the potential impact of SPCA1 on neuronal polarization both in a cell line and in primary neuronal culture. In N2a neuroblastoma cells, SPCA1 was immunocytochemically localized in the juxtanuclear Golgi. Knockdown of SPCA1 by RNA interference markedly delayed the differentiation in these cells. The cells retarded in differentiation showed increased numbers of neurites of reduced length compared with control cells. Ca 2ϩ imaging assays showed that the lack of SPCA1 impaired Golgi Ca 2ϩ homeostasis and resulted in disturbed trafficking of different classes of proteins including normally Golgi-localized cameleon GT-YC3.3, bearing a Golgi-specific galactosyltransferase N terminus, and a normally plasma membrane-targeted, glycosyl phosphatidyl inositol-anchored cyan fluorescent protein construct. Also in hippocampal primary neurons, which showed a differential distribution of SPCA1 expression in Golgi stacks depending on differentiation stage, partial silencing of SPCA1 resulted in delayed differentiation, whereas total suppression drastically affected the cell survival. The disturbed overall cellular Ca 2ϩ homeostasis and/or the altered targeting of organellar proteins under conditions of SPCA1 knockdown highlight the importance of SPCA1 function for normal neural differentiation.

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“…These results are comparable to those found in adult tissue (Fig. 5C) and also to those described in postnatal developing mouse hippocampal tissue (Sepú lveda et al, 2008).…”

Section: Suppression Of Spca1 In Mouse Hippocampal Neurons Also Impaisupporting

confidence: 91%

Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 94%

See 1 more Smart Citation

Silencing the SPCA1 (Secretory Pathway Ca²⁺-ATPase Isoform 1) Impairs Ca²⁺Homeostasis in the Golgi and Disturbs Neural Polarity

Sepúlveda¹,

Vanoevelen²,

Raeymaekers³

et al. 2009

J. Neurosci.

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“…In spite of the apparently unchanged expression levels, SPCA-associated Ca 2þ -ATPase activity increased with the stage of development (Sepulveda et al 2008). SPCA1 was localized in Golgi stacks of the soma and the initial part of the primary dendritic trunk in main cortical, hippocampal and cerebellar neurons, and is present from the earliest postnatal stages onward.…”

Section: Spca1mentioning

confidence: 95%

“…SPCA1 was localized in Golgi stacks of the soma and the initial part of the primary dendritic trunk in main cortical, hippocampal and cerebellar neurons, and is present from the earliest postnatal stages onward. Although SPCA1 expression has been reported in different glial cultures (Murin et al 2006), other efforts to show SPCA-or SERCA-pump expression in glial cells in nervous tissue were unsuccessful (Baba-Aissa et al 1996b;Sepulveda et al 2007;Sepulveda et al 2008). Because glial cells express high levels of the Mn 2þ -dependent glutamine synthetase (Wedler and Denman 1984), the low levels of SPCAs argues against a role of SPCAs in Mn 2þ uptake.…”

Section: Spca1mentioning

confidence: 99%

The Ca2+ Pumps of the Endoplasmic Reticulum and Golgi Apparatus

Vandecaetsbeek

Vangheluwe²,

Raeymaekers³

et al. 2011

Cold Spring Harbor Perspectives in Biology

186

170

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The various splice variants of the three SERCA-and the two SPCA-pump genes in higher vertebrates encode P-type ATPases of the P 2A group found respectively in the membranes of the endoplasmic reticulum and the secretory pathway. Of these, SERCA2b and SPCA1a represent the housekeeping isoforms. The SERCA2b form is characterized by a luminal carboxy terminus imposing a higher affinity for cytosolic Ca 2þ compared to the other SERCAs. This is mediated by intramembrane and luminal interactions of this extension with the pump. Other known affinity modulators like phospholamban and sarcolipin decrease the affinity for Ca 2þ . The number of proteins reported to interact with SERCA is rapidly growing. Here, we limit the discussion to those for which the interaction site with the ATPase is specified: HAX-1, calumenin, histidine-rich Ca 2þ -binding protein, and indirectly calreticulin, calnexin, and ERp57. The role of the phylogenetically older and structurally simpler SPCAs as transporters of Ca 2þ , but also of Mn 2þ , is also addressed.

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Evaluation of manganese uptake and toxicity in mouse brain during continuous MnCl₂ administration using osmotic pumps

Sepúlveda

Dresselaers

Vangheluwe

et al. 2012

Contrast Media & Molecular

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Manganese is a vital element and cofactor of many key enzymes, but it is toxic at high levels, causing pronounced disturbances in the mammalian brain. Magnetic resonance imaging (MRI) studies using manganese ions as a paramagnetic contrast agent are often limited by the neurotoxicity of Mn(2+) . In this work, we have explored a new in vivo model to study Mn(2+) uptake, distribution and neurotoxicity in mice by subcutaneous implantation of mini-osmotic pumps delivering MnCl(2) continuously for 21 days. Fractionated injections can reduce the toxicity; however, constant administration at very low doses using osmotic pumps caused a substantial effect on the T(1) contrast in MRI while reducing toxicity. Manganese-enhanced MRI documented fast but reversible Mn(2+) deposition largely in glomerular and mitral cell layers of the olfactory bulb, in the CA3 area of the hippocampus, and in the gray matter of the cerebellum. Mn(2+) accumulated as early as the first days after implantation, with a fast dispersal 9 days after stopping a 12-days Mn(2+) exposure. Prominent Mn(2+) accumulation was also seen in salivary glands and in the endocrine thyroid and posterior pituitary gland. These structures with enhanced Mn(2+) accumulation correlated well with those showing high expression of the secretory pathway Ca(2+) /Mn(2+) -ATPase (SPCA1), i.e. a transporter that could take part in Mn(2+) detoxification. Our new experimental model for continuous low-dosage administration of Mn(2+) is an easy alternative for enhancing Mn(2+) -based contrast in MEMRI studies, and might provide insight into the etiology of neuropathologies resulting from chronic Mn(2+) exposure in vivo.

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Activity and localization of the Secretory Pathway Ca2+-ATPase isoform 1 (SPCA1) in different areas of the mouse brain during postnatal development

Cited by 29 publications

References 34 publications

Silencing the SPCA1 (Secretory Pathway Ca²⁺-ATPase Isoform 1) Impairs Ca²⁺Homeostasis in the Golgi and Disturbs Neural Polarity

Silencing the SPCA1 (Secretory Pathway Ca²⁺-ATPase Isoform 1) Impairs Ca²⁺Homeostasis in the Golgi and Disturbs Neural Polarity

The Ca2+ Pumps of the Endoplasmic Reticulum and Golgi Apparatus

Evaluation of manganese uptake and toxicity in mouse brain during continuous MnCl₂ administration using osmotic pumps

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Activity and localization of the Secretory Pathway Ca2+-ATPase isoform 1 (SPCA1) in different areas of the mouse brain during postnatal development

Cited by 29 publications

References 34 publications

Silencing the SPCA1 (Secretory Pathway Ca2+-ATPase Isoform 1) Impairs Ca2+Homeostasis in the Golgi and Disturbs Neural Polarity

Silencing the SPCA1 (Secretory Pathway Ca2+-ATPase Isoform 1) Impairs Ca2+Homeostasis in the Golgi and Disturbs Neural Polarity

The Ca2+ Pumps of the Endoplasmic Reticulum and Golgi Apparatus

Evaluation of manganese uptake and toxicity in mouse brain during continuous MnCl2 administration using osmotic pumps

Contact Info

Product

Resources

About

Silencing the SPCA1 (Secretory Pathway Ca²⁺-ATPase Isoform 1) Impairs Ca²⁺Homeostasis in the Golgi and Disturbs Neural Polarity

Silencing the SPCA1 (Secretory Pathway Ca²⁺-ATPase Isoform 1) Impairs Ca²⁺Homeostasis in the Golgi and Disturbs Neural Polarity

Evaluation of manganese uptake and toxicity in mouse brain during continuous MnCl₂ administration using osmotic pumps