Calcium pump disorders of the skin

Foggia, L.; Hovnanian, Alain

doi:10.1002/ajmg.c.30031

Cited by 71 publications

(69 citation statements)

References 71 publications

(80 reference statements)

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“…The co-expression of hSPCA2 and hSPCA1 could help to explain the relatively high contribution of thapsigargininsensitive Ca 2ϩ accumulation in the Golgi of keratinocytes (33) and lung-derived 16HBE14oϪ cells (34). The proper function of the secretory pathway in keratinocytes may be crucial for correct delivery of cell adhesion components (15). The fact that hSPCA2 is not able to compensate for the decreased level of hSPCA1 in keratinocytes of Hailey-Hailey disease patients may suggest a specific function for this pump distinct from that of hSPCA1.…”

Section: Discussionmentioning

confidence: 99%

“…Hailey-Hailey disease is an autosomal dominant skin disorder that is characterized by suprabasal acantholysis of keratinocytes, resulting in epidermal blister formation. Up till now a total of 70 different mutations have been described in Hailey-Hailey disease patients (15). These mutations are scattered throughout the entire gene with no apparent clustering.…”

Section: ؉mentioning

confidence: 99%

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The Secretory Pathway Ca2+/Mn2+-ATPase 2 Is a Golgi-localized Pump with High Affinity for Ca2+ Ions

Vanoevelen

Dode

Baelen

et al. 2005

Journal of Biological Chemistry

121

124

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Section: Discussionmentioning

confidence: 99%

Section: ؉mentioning

confidence: 99%

The Secretory Pathway Ca2+/Mn2+-ATPase 2 Is a Golgi-localized Pump with High Affinity for Ca2+ Ions

Vanoevelen

Dode

Baelen

et al. 2005

Journal of Biological Chemistry

121

124

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“…In contrast to SERCAs, SPCAs are also equipped to transport Mn 2þ and thus supply this essential trace metal to the Golgi lumen. A number of comprehensive reviews have been published recently by our group Vangheluwe et al 2009) and by others (Dhitavat et al 2004;Foggia and Hovnanian 2004;Brini and Carafoli 2009). …”

Section: Spcasmentioning

confidence: 92%

The Ca2+ Pumps of the Endoplasmic Reticulum and Golgi Apparatus

Vandecaetsbeek

Vangheluwe²,

Raeymaekers³

et al. 2011

Cold Spring Harbor Perspectives in Biology

184

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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“…In humans, it has been suggested that HHD and Darier disease may result from defective processing and trafficking of desmosomal components (63). In the case of HHD, this mechanism seems unlikely, since desmosomes and other cell surface structures appeared normal in null mutant mice.…”

Section: Squamous Cell Tumors In Spca1 Heterozygous Micespca1mentioning

confidence: 99%

Loss of the Atp2c1 Secretory Pathway Ca2+-ATPase (SPCA1) in Mice Causes Golgi Stress, Apoptosis, and Midgestational Death in Homozygous Embryos and Squamous Cell Tumors in Adult Heterozygotes

Okunade

Miller

Azhar

et al. 2007

Journal of Biological Chemistry

110

124

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embryos had an open rostral neural tube, but hematopoiesis and cardiovascular development were ostensibly normal. Golgi membranes of Spca1 ؊/؊ embryos were dilated, had fewer stacked leaflets, and were expanded in amount, consistent with increased Golgi biogenesis. The number of Golgi-associated vesicles was also increased, and rough endoplasmic reticulum had fewer ribosomes. Coated pits, junctional complexes, desmosomes, and basement membranes appeared normal in mutant embryos, indicating that processing and trafficking of proteins in the secretory pathway was not massively impaired. However, apoptosis was increased, possibly the result of secretory pathway stress, and a large increase in cytoplasmic lipid was observed in mutant embryos, consistent with impaired handling of lipid by the Golgi. Adult heterozygous mice appeared normal and exhibited no evidence of Hailey-Hailey disease; however, aged heterozygotes had an increased incidence of squamous cell tumors of keratinized epithelial cells of the skin and esophagus. These data show that loss of the Golgi Ca 2؉ pump causes Golgi stress, expansion of the Golgi, increased apoptosis, and embryonic lethality and demonstrates that SPCA1 haploinsufficiency causes a genetic predisposition to cancer. and Mn 2ϩ (10). Loss of PMR1 affects outer chain glycosylation, proteolytic processing, and trafficking of proteins in the secretory pathway (9). In mammals, SPCA1 is expressed in all tissues (1), whereas SPCA2 is expressed in only a limited set of tissues (3). Like PMR1, both SPCA1 and SPCA2 are localized to the Golgi and transport Ca 2ϩ and Mn 2ϩ (3, 11). There is evidence that the cell biological functions of SPCA1 are also similar to those of PMR1 (12).Loss of one copy of the human ATP2C1 gene, encoding SPCA1, causes Hailey-Hailey disease (HHD), an autosomal dominant skin disorder (13,14). SPCA1 protein levels in HHD keratinocytes are reduced to about half of normal levels, and Golgi Ca 2ϩ handling is impaired (15). HHD is similar to Darier disease, which is caused by null mutations in one copy of the human ATP2A2 gene, encoding SERCA2 (16). Both diseases are characterized by acantholysis (a disruption of cell-cell contacts) in the suprabasal layers of the skin. As the major ER Ca 2ϩ pump in most tissues, including keratinocytes, the function of SERCA2 is similar to that of SPCA1 in that it maintains luminal Ca 2ϩ concentrations in a major compartment of the secretory pathway. In mice, SERCA2 haploinsufficiency does not cause Darier disease but does lead to squamous cell tumors of keratinized epithelial cells (17, 18), the same cell type affected in Darier disease. In humans, a low incidence of squamous cell tumors has been reported in both Darier disease (19) and HHD (20, 21), but it is unclear whether this is a chance association or is caused by the reduction in Ca 2ϩ pump levels and activity. In the current study, we developed a gene-targeted mouse model for SPCA1 and analyzed the phenotype resulting from heterozygous and homozygous null mutations. The results sho...

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Calcium pump disorders of the skin

Cited by 71 publications

References 71 publications

The Secretory Pathway Ca2+/Mn2+-ATPase 2 Is a Golgi-localized Pump with High Affinity for Ca2+ Ions

The Secretory Pathway Ca2+/Mn2+-ATPase 2 Is a Golgi-localized Pump with High Affinity for Ca2+ Ions

The Ca2+ Pumps of the Endoplasmic Reticulum and Golgi Apparatus

Loss of the Atp2c1 Secretory Pathway Ca2+-ATPase (SPCA1) in Mice Causes Golgi Stress, Apoptosis, and Midgestational Death in Homozygous Embryos and Squamous Cell Tumors in Adult Heterozygotes

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