An apical expression signal of the renal type IIc Na+-dependent phosphate cotransporter in renal epithelial cells

作者：Ito Mikiko; Sakurai Aya; Hayashi Keiji; Ohi Akiko; Kangawa Natsumi; Nishiyama Takashi; Sugino Sakiko; Uehata Yoko; Kamahara Akihiro; Sakata Masae; Tatsumi Sawako; Kuwahata Masashi; Taketani Yutaka; Segawa Hiroko; Miyamoto Ken ichi^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2010, 299(1): F243-F254.

DOI：10.1152/ajprenal.00189.2009

• Npt2c
• SLC34A3
• localization
• OK cell
• hereditary hypophosphatemic rickets with hypercalciuria

Ito M, Sakurai A, Hayashi K, Ohi A, Kangawa N, Nishiyama T, Sugino S, Uehata Y, Kamahara A, Sakata M, Tatsumi S, Kuwahata M, Taketani Y, Segawa H, Miyamoto K. An apical expression signal of the renal type IIc Na+-dependent phosphate cotransporter in renal epithelial cells. Am J Physiol Renal Physiol 299: F243-F254, 2010. First published April 21, 2010; doi: 10.1152/ajprenal.00189.2009.-The type IIc Na+-dependent phosphate cotransporter (NaPi-IIc) is specifically targeted to, and expressed on, the apical membrane of renal proximal tubular cells and mediates phosphate transport. In the present study, we investigated the signals that determine apical expression of NaPi-IIc with a focus on the role of the N- and the C-terminal tails of mouse NaPi-IIc in renal epithelial cells [opossum kidney (OK) and Madin-Darby canine kidney cells]. Wild-type NaPi-IIc, the cotransporter NaPi-IIa, as well as several IIa-IIc chimeras and deletion mutants, were fused to enhanced green fluorescent protein (EGFP), and their cellular localization was analyzed in polarized renal epithelial cells by confocal microscopy and by cell-surface biotinylation. Fluorescent EGFP-fused NaPi-IIc transporter proteins are correctly expressed in the apical membrane of OK cells. The apical expression of N-terminal deletion mutants (deletion of N-terminal 25, 50, or 69 amino acids) was not affected by truncation. In contrast, C-terminal deletion mutants (deletion of C-terminal 45, 50, or 62 amino acids) did not have correct apical expression. A more detailed mutational analysis indicated that a domain (amino acids WLHSL) in the cytoplasmic C terminus is required for apical expression of NaPi-IIc in renal epithelial cells. We conclude that targeting of NaPi-IIc to the apical cell surface is regulated by a unique amino acid motif in the cytoplasmic C-terminal domain.

• 出版日期2010-7