title: Tyrosine motifs are required for prestin basolateral membrane targeting.
abstract: Prestin is targeted to the lateral wall of outer hair cells (OHCs) where its electromotility is critical for cochlear amplification. Using MDCK cells as a model system for polarized epithelial sorting, we demonstrate that prestin uses tyrosine residues, in a YXXΦ motif, to target the basolateral surface. Both Y520 and Y667 are important for basolateral targeting of prestin. Mutation of these residues to glutamine or alanine resulted in retention within the Golgi and delayed egress from the Golgi in Y667Q. Basolateral targeting is restored upon mutation to phenylalanine suggesting the importance of a phenol ring in the tyrosine side chain. We also demonstrate that prestin targeting to the basolateral surface is dependent on AP1B (μ1B), and that prestin uses transferrin containing early endosomes in its passage from the Golgi to the basolateral plasma membrane. The presence of AP1B (μ1B) in OHCs, and parallels between prestin targeting to the basolateral surface of OHCs and polarized epithelial cells suggest that outer hair cells resemble polarized epithelia rather than neurons in this important phenotypic measure.
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Iman
authors.initials: I
authors.lastname: Moeini-Naghani
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: JunPing
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, CT 06510, USA Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Santos-Sacchi
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA Department of Surgery, Yale School of Medicine, New Haven, CT 06510, USA Dhasakumar.Navaratnam@Yale.Edu.
authors.forename: Dhasakumar S
authors.initials: DS
authors.lastname: Navaratnam
keywords: Cell polarity; Golgi; Hair cell; Protein sorting; Tyrosine