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Homer2 Protein Regulates Plasma Membrane Ca2+ ATPase -mediated Ca2+ Signaling in Mouse Parotid Gland Acinar Cells

 Yu-Mi Yang  ;  Jiae Lee  ;  Hae Jo  ;  Soonhong Park  ;  Inik Chang  ;  Shmuel Muallem  ;  Dong Min Shin 
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.289(36) : 24971-24979, 2014 
Journal Title
Issue Date
Acinar Cells/metabolism* ; Amino Acid Sequence ; Animals ; Binding Sites/genetics ; Blotting, Western ; Calcium/metabolism* ; Calcium Signaling ; Carrier Proteins/genetics ; Carrier Proteins/metabolism* ; HEK293 Cells ; Homer Scaffolding Proteins ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Mice, Knockout ; Microscopy, Confocal ; Molecular Sequence Data ; Parotid Gland/cytology ; Parotid Gland/metabolism* ; Plasma Membrane Calcium-Transporting ATPases/genetics ; Plasma Membrane Calcium-Transporting ATPases/metabolism* ; Protein Binding ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism ; Sequence Homology, Amino Acid
Calcium ATPase ; Calcium Transport ; Cell Signaling ; Homer Proteins ; Parotid Gland ; Plasma Membrane Ca2+-ATPase ; Proline-rich Motif ; Protein-Protein Interaction ; Scaffold Protein
Homer proteins are scaffold molecules with a domain structure consisting of an N-terminal Ena/VASP homology 1 protein-binding domain and a C-terminal leucine zipper/coiled-coil domain. The Ena/VASP homology 1 domain recognizes proline-rich motifs and binds multiple Ca(2+)-signaling proteins, including G protein-coupled receptors, inositol 1,4,5-triphosphate receptors, ryanodine receptors, and transient receptor potential channels. However, their role in Ca(2+) signaling in nonexcitable cells is not well understood. In this study, we investigated the role of Homer2 on Ca(2+) signaling in parotid gland acinar cells using Homer2-deficient (Homer2(-/-)) mice. Homer2 is localized at the apical pole in acinar cells. Deletion of Homer2 did not affect inositol 1,4,5-triphosphate receptor localization or channel activity and did not affect the expression and activity of sarco/endoplasmic reticulum Ca(2+)-ATPase pumps. In contrast, Homer2 deletion markedly increased expression of plasma membrane Ca(2+)-ATPase (PMCA) pumps, in particular PMCA4, at the apical pole. Accordingly, Homer2 deficiency increased Ca(2+) extrusion by acinar cells. These findings were supported by co-immunoprecipitation of Homer2 and PMCA in wild-type parotid cells and transfected human embryonic kidney 293 (HEK293) cells. We identified a Homer-binding PPXXF-like motif in the N terminus of PMCA that is required for interaction with Homer2. Mutation of the PPXXF-like motif did not affect the interaction of PMCA with Homer1 but inhibited its interaction with Homer2 and increased Ca(2+) clearance by PMCA. These findings reveal an important regulation of PMCA by Homer2 that has a central role on PMCA-mediated Ca(2+) signaling in parotid acinar cells.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Soon Hong(박순홍)
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
Yang, Yu Mi(양유미)
Lee, Ji Ae(이지애)
Chang, In Ik(장인익)
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