title: Ankyrin-B directs membrane tethering of periaxin and is required for maintenance of lens fiber cell hexagonal shape and mechanics.
abstract: Periaxin (Prx), a PDZ domain protein expressed preferentially in myelinating Schwann cells and lens fibers, plays a key role in membrane scaffolding and cytoarchitecture. Little is known, however, about how Prx is anchored to the plasma membrane. Here we report that ankyrin-B (AnkB), a well-characterized adaptor protein involved in linking the spectrin-actin cytoskeleton to integral membrane proteins, is required for membrane association of Prx in lens fibers and colocalizes with Prx in hexagonal fiber cells. Under AnkB haploinsufficiency, Prx accumulates in the soluble fraction with a concomitant loss from the membrane-enriched fraction of mouse lenses. Moreover, AnkB haploinsufficiency induced age-dependent disruptions in fiber cell hexagonal geometry and radial alignment and decreased compressive stiffness in mouse lenses parallel to the changes observed in Prx null mouse lens. Both AnkB- and Prx-deficient mice exhibit disruptions in membrane organization of the spectrin-actin network and the dystrophin-glycoprotein complex in lens fiber cells. Taken together, these observations reveal that AnkB is required for Prx membrane anchoring and for maintenance of lens fiber cell hexagonal geometry, membrane skeleton organization, and biomechanics.
authors.affiliation: Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina;
authors.forename: Rupalatha
authors.initials: R
authors.lastname: Maddala
authors.affiliation: Department of Mechanical Engineering and Materials Science, Pratt School of Engineering, Duke University, Durham, North Carolina;
authors.forename: Mark
authors.initials: M
authors.lastname: Walters
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom;
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brophy
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, Maryland; Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina; and.
authors.forename: Vann
authors.initials: V
authors.lastname: Bennett
authors.affiliation: Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina p.rao@dm.duke.edu.
authors.forename: Ponugoti V
authors.initials: PV
authors.lastname: Rao
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane; D048429:Cell Size; D019245:Compressive Strength / Q000502:physiology; D055119:Elastic Modulus / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006244:Hardness / Q000502:physiology; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000166:cytology* / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000502:physiology
chemical_list: D017487:Ankyrins; D008565:Membrane Proteins; C086745:periaxin
keywords: ankyrin-B; cytoarchitecture; dystrophin; lens fibers; periaxin; stiffness