title: GAR22β regulates cell migration, sperm motility, and axoneme structure.
abstract: Spatiotemporal cytoskeleton remodeling is pivotal for cell adhesion and migration. Here we investigated the function of Gas2-related protein on chromosome 22 (GAR22β), a poorly characterized protein that interacts with actin and microtubules. Primary and immortalized GAR22β(-/-) Sertoli cells moved faster than wild-type cells. In addition, GAR22β(-/-) cells showed a more prominent focal adhesion turnover. GAR22β overexpression or its reexpression in GAR22β(-/-) cells reduced cell motility and focal adhesion turnover. GAR22β-actin interaction was stronger than GAR22β-microtubule interaction, resulting in GAR22β localization and dynamics that mirrored those of the actin cytoskeleton. Mechanistically, GAR22β interacted with the regulator of microtubule dynamics end-binding protein 1 (EB1) via a novel noncanonical amino acid sequence, and this GAR22β-EB1 interaction was required for the ability of GAR22β to modulate cell motility. We found that GAR22β is highly expressed in mouse testes, and its absence resulted in reduced spermatozoa generation, lower actin levels in testes, and impaired motility and ultrastructural disorganization of spermatozoa. Collectively our findings identify GAR22β as a novel regulator of cell adhesion and migration and provide a foundation for understanding the molecular basis of diverse cytoskeleton-dependent processes.
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, D-52074 Aachen, Germany Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Gamper
authors.affiliation: Institute for Biology II, Department of Chemosensation, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Fleck
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, D-52074 Aachen, Germany Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Meltem
authors.initials: M
authors.lastname: Barlin
authors.affiliation: Institute for Biology II, Department of Chemosensation, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Spehr
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, D-52074 Aachen, Germany Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: El Sayad
authors.affiliation: Institute of Biochemistry and Molecular Biology, Uniklinik RWTH Aachen, D-52074 Aachen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Kleine
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, D-52074 Aachen, Germany Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Maxeiner
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, D-52074 Aachen, Germany Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Schalla
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, D-52074 Aachen, Germany Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Gülcan
authors.initials: G
authors.lastname: Aydin
authors.affiliation: Electron Microscopy Facility, Uniklinik RWTH Aachen, D-52074 Aachen, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Hoss
authors.affiliation: Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Litchfield
authors.affiliation: Institute of Biochemistry and Molecular Biology, Uniklinik RWTH Aachen, D-52074 Aachen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lüscher
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, D-52074 Aachen, Germany Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, D-52074 Aachen, Germany Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, D-52074 Aachen, Germany Antonio.Sechi@rwth-aachen.de.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sechi
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D054468:Axoneme / Q000378:metabolism / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D013081:Sperm Motility / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins