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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 Ca2+-signaling proteins, including G protein-coupled receptors, inositol 1,4,5-triphosphate receptors, ryanodine receptors, and transient receptor potential channels. However, their role in Ca2+signaling in nonexcitable cells is not well understood. In this study, we investigated the role of Homer2 on Ca2+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 Ca2+-ATPase pumps. In contrast, Homer2 deletion markedly increased expression of plasma membrane Ca2+-ATPase (PMCA) pumps, in particular PMCA4, at the apical pole. Accordingly, Homer2 deficiency increased Ca2+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 Ca2+clearance by PMCA. These findings reveal an important regulation of PMCA by Homer2 that has a central role on PMCA-mediated Ca2+signaling in parotid acinar cells.

Original languageEnglish
Pages (from-to)24971-24979
Number of pages9
JournalJournal of Biological Chemistry
Volume289
Issue number36
DOIs
Publication statusPublished - 2014 Jan 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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