Unraveling the molecular basis of mammalian inner ear evolution: analysis of the outer hair cell cytoskeleton protein spectrin

PISCIOTTANO FRANCISCO; ANA BELÉN ELGOYHEN; FRANCHINI LF

Oro Verde

Congreso; 3er Congreso Argentino de Bioinformática y Biología Computacional; 2012

In our laboratory we are studying the genetic basis underlying the evolution of the particular functional capacities of the mammalian inner ear. During the evolution of mammals, the inner ear went through many important changes that made it different from the hearing organ of other vertebrates and endowed mammals with unique hearing capacities in the animal kingdom. Among many changes we can remark the origin of a unique cellular type, the outer hair cell (OHC), which shows a novel mechanism known as somatic electromotility. This mechanism of mechanic amplification is an active cochlear amplifier that can increase hearing sensitivity and frequency selectivity and depends on OHCs length changes mediated by the motor protein prestin. These length changes are possible due to the particular characteristics of the OHC's lateral wall, which has a submembranous lateral system, known as cortical lattice. This protein based skeleton consists of circumferential filaments of actin that are cross-linked with filaments of spectrin. In the cortical lattice of the mammalian OHCs alphaII-spectrin in found in association with betaV-spectrin, which indirectly interacts with prestin [1]. We found in previous work that prestin shows strong signatures of positive selection in the mammalian lineage [2]. Using maximum likelihood methods to test models of positive selection we aim to reveal which other proteins were involved in shaping the morphological and functional particularities of the mammalian inner ear. Our present results suggest that betaV-spectrin has accompanied prestin?s evolutionary trend in the lineage leading to mammals. Moreover, betaV-spectrin selected sites group in clusters which show to distribute non-randomly along the protein spanning over specific spectrin domains. Among the domains that accumulate positive selected amino-acids we find those mediating interaction with alphaII-spectrin for dimerization and with the adaptor proteins ankyrin, which mediate the attachment on integral membrane proteins to the spectrin-actin based membrane skeleton. Our work continues to delineate the genetic bases underlying the evolution of the inner ear in mammals. References 1. Legendre K, Safieddine S, Küssel-Andermann P, Petit C, El-Amraoui A: αII-βV spectrin bridgesthe plasma membrane and cortical lattice in the lateral wall of the auditory outer hair cells. J CellSci. 2008, 121:3347-3356. 2. Franchini LF, Elgoyhen AB: Adaptive evolution in mammalian proteins involved in cochlear outer hair cell electromotility. Mol Phylogenet Evol 2006, 41:622-635.