Spectrin βV adaptive mutations and changes in subcellular location correlate with emergence of hair cell electromotility in mammalians.
The remarkable hearing capacities of mammals arise from various evolutionary innovations. These include the cochlear outer hair cells and their singular feature, somatic electromotility, i.e., the ability of their cylindrical cell body to shorten and elongate upon cell depolarization and hyperpolarization, respectively. To shed light on the processes underlying the emergence of electromotility, we focused on the βV giant spectrin, a major component of the outer hair cells' cortical cytoskeleton. We identified strong signatures of adaptive evolution at multiple sites along the spectrin-βV amino acid sequence in the lineage leading to mammals, together with substantial differences in the subcellular location of this protein between the frog and the mouse inner ear hair cells. In frog hair cells, spectrin βV was invariably detected near the apical junctional complex and above the cuticular plate, a dense F-actin meshwork located underneath the apical plasma membrane. In the mouse, the protein had a broad punctate cytoplasmic distribution in the vestibular hair cells, whereas it was detected in the entire lateral wall of cochlear outer hair cells and had an intermediary distribution (both cytoplasmic and cortical, but restricted to the cell apical region) in cochlear inner hair cells. Our results support a scenario where the singular organization of the outer hair cells' cortical cytoskeleton may have emerged from molecular networks initially involved in membrane trafficking, which were present near the apical junctional complex in the hair cells of mammalian ancestors and would have subsequently expanded to the entire lateral wall in outer hair cells.
Génétique et Physiologie de l'Audition, Institut Pasteur, F-75015 Paris, France.|Unité Mixte de Recherche, UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), F-75013 Paris, France.|Complexité du vivant, UPMC Université Paris 06, Sorbonne Universités, F-75005 Paris, France.
Matteo
M
Cortese
Génétique et Physiologie de l'Audition, Institut Pasteur, F-75015 Paris, France.|Unité Mixte de Recherche, UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), F-75013 Paris, France.|Complexité du vivant, UPMC Université Paris 06, Sorbonne Universités, F-75005 Paris, France.
Samantha
S
Papal
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres" (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428ADN Buenos Aires, Argentina.
Francisco
F
Pisciottano
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres" (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428ADN Buenos Aires, Argentina.|Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, C1121ABG Buenos Aires, Argentina.
Ana Belén
AB
Elgoyhen
Génétique et Physiologie de l'Audition, Institut Pasteur, F-75015 Paris, France.|Unité Mixte de Recherche, UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), F-75013 Paris, France.|Complexité du vivant, UPMC Université Paris 06, Sorbonne Universités, F-75005 Paris, France.
Jean-Pierre
JP
Hardelin
Génétique et Physiologie de l'Audition, Institut Pasteur, F-75015 Paris, France.|Unité Mixte de Recherche, UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), F-75013 Paris, France.|Complexité du vivant, UPMC Université Paris 06, Sorbonne Universités, F-75005 Paris, France.|Collège de France, F-75005 Paris, France.
Christine
C
Petit
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres" (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428ADN Buenos Aires, Argentina; aziz.el-amraoui@pasteur.fr franchini@dna.uba.ar.
Lucia Florencia
LF
Franchini
Génétique et Physiologie de l'Audition, Institut Pasteur, F-75015 Paris, France; aziz.el-amraoui@pasteur.fr franchini@dna.uba.ar.|Unité Mixte de Recherche, UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), F-75013 Paris, France.|Complexité du vivant, UPMC Université Paris 06, Sorbonne Universités, F-75005 Paris, France.
Aziz
A
El-Amraoui
D000199:Actins / Q000378:metabolism; D000220:Adaptation, Biological / Q000235:genetics; D000818:Animals; D001717:Birds / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D003198:Computer Simulation; D055724:Electrophysiological Phenomena; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D018072:Hair Cells, Auditory, Outer / Q000502:physiology*; D006367:HeLa Cells; D006309:Hearing / Q000502:physiology; D006801:Humans; D008322:Mammals / Q000502:physiology*; D051379:Mice; D009154:Mutation; D010802:Phylogeny; D013049:Spectrin / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000502:physiology
D000199:Actins; D013049:Spectrin
F-actin cytoskeleton; cortical lattice; inner ear; phylogenetics; unconventional spectrins