CLC-2 chloride channel localizes to the apical membrane and the primary cilium in polarized RPE cells

IÑAQUI BENEDICTO; S SALFATI; GUILLERMO LEHMANN; DIEGO GRAVOTTA; ENRIQUE RODRIGUEZ BOULAN; ERWIN DE LA FUENTE; AGUSTIN ANASTASIA

La Serena

Workshop; EMBO workshop: Actualization in membrane trafficking in health and disease?; 2016

EMBO

The chloride channel 2 (ClC-2) is a polytopic membrane protein ubiquitously expressed in the human body that plays important physiological roles in cell volume regulation, ion transport and acid-base balance (Jentsch et al., 2005; Strauss, 2005). A major task of the RPE is to transport a net amount of fluid in the apical to basal direction, creating a negative pressure that helps attach the neural retina to the RPE (Adijanto et al., 2009) driven by the transepithelial absorption of KCl. There is functional evidence based on pharmacologic manipulation of Cl- conductance that suggests that ClC-2 is baso- laterally localized in RPE. Knock-out of this channel in mice causes retinal degeneration, suggesting that ClC-2 is in- volved in retinal homeostasis (Bosl et al., 2001). However, the domain-speci¬c localization of ClC-2 in polarized RPE cells has not been addressed yet. Contrary to what is expected, localization of CLC-2 in RPE cells is primarily apical and it is enriched in the primary cilium, where it seems to play a role in the formation of the cilia and cell signaling. The PC location of CLC-2 opens the exciting possibility that ClC-2 has an important role in RPE physiology from this location.