SPCA2 regulates Orai1 trafficking and store independent Ca2+ entry in a model of lactation

Autor: Anniesha Hack, Rajini Rao, Brandie M. Cross, Timothy A. Reinhardt
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Anatomy and Physiology
ORAI1 Protein
Cellular differentiation
lcsh:Medicine
Biochemistry
Ion Channels
Transmembrane Transport Proteins
Mice
0302 clinical medicine
Molecular Cell Biology
Protein Isoforms
Signaling in Cellular Processes
lcsh:Science
Calcium signaling
0303 health sciences
Multidisciplinary
Voltage-dependent calcium channel
ORAI1
Obstetrics and Gynecology
Signaling Cascades
Cellular Structures
Cell biology
Transport protein
Protein Transport
medicine.anatomical_structure
Breast Feeding
030220 oncology & carcinogenesis
Gene Knockdown Techniques
symbols
Medicine
Female
Membranes and Sorting
Cellular Types
Transmembrane Signaling
Research Article
Signal Transduction
Cell Physiology
Mice
129 Strain
Calcium-Transporting ATPases
Biology
Signaling Pathways
03 medical and health sciences
symbols.namesake
Mammary Glands
Animal
Spheroids
Cellular
medicine
Calcium-Mediated Signal Transduction
Animals
Humans
Lactation
Calcium Signaling
Secretory pathway
030304 developmental biology
lcsh:R
Proteins
Golgi apparatus
Epithelium
Protein Structure
Tertiary
Transmembrane Proteins
HEK293 Cells
Calcium Signaling Cascade
Women's Health
Calcium
lcsh:Q
Calcium Channels
Zdroj: PLoS ONE, Vol 8, Iss 6, p e67348 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: An unconventional interaction between SPCA2, an isoform of the Golgi secretory pathway Ca(2+)-ATPase, and the Ca(2+) influx channel Orai1, has previously been shown to contribute to elevated Ca(2+) influx in breast cancer derived cells. In order to investigate the physiological role of this interaction, we examined expression and localization of SPCA2 and Orai1 in mouse lactating mammary glands. We observed co-induction and co-immunoprecipitation of both proteins, and isoform-specific differences in the localization of SPCA1 and SPCA2. Three-dimensional cultures of normal mouse mammary epithelial cells were established using lactogenic hormones and basement membrane. The mammospheres displayed elevated Ca(2+) influx by store independent mechanisms, consistent with upregulation of both SPCA2 and Orai1. Knockdown of either SPCA2 or Orai1 severely depleted Ca(2+) influx and interfered with mammosphere differentiation. We show that SPCA2 is required for plasma membrane trafficking of Orai1 in mouse mammary epithelial cells and that this function can be replaced, at least in part, by a membrane-anchored C-terminal domain of SPCA2. These findings clearly show that SPCA2 and Orai1 function together to regulate Store-independent Ca(2+) entry (SICE), which mediates the massive basolateral Ca(2+) influx into mammary epithelia to support the large calcium transport requirements for milk secretion.
Databáze: OpenAIRE
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