title: ANKS4B Is Essential for Intermicrovillar Adhesion Complex Formation.
abstract: Transporting and sensory epithelial cells shape apical specializations using protocadherin-based adhesion. In the enterocyte brush border, protocadherin function requires a complex of cytoplasmic binding partners, although the composition of this complex and logic governing its assembly remain poorly understood. We found that ankyrin repeat and sterile α motif domain containing 4B (ANKS4B) localizes to the tips of adherent brush border microvilli and is essential for intermicrovillar adhesion. ANKS4B interacts with USH1C and MYO7B, which link protocadherins to the actin cytoskeleton. ANKS4B and USH1C also bind to the MYO7B cargo-binding tail at distinct sites. However, a tripartite complex only forms if ANKS4B and MYO7B are first activated by USH1C. This study uncovers an essential role for ANKS4B in brush border assembly, reveals a hierarchy in the molecular interactions that drive intermicrovillar adhesion, and informs our understanding of diseases caused by mutations in USH1C and ankyrin repeat proteins, such as Usher syndrome.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 3154 MRB III, PMB 407935, 465 21(st) Avenue South, Nashville, TN 37240-7935, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Crawley
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 3154 MRB III, PMB 407935, 465 21(st) Avenue South, Nashville, TN 37240-7935, USA.
authors.forename: Meredith L
authors.initials: ML
authors.lastname: Weck
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 3154 MRB III, PMB 407935, 465 21(st) Avenue South, Nashville, TN 37240-7935, USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Grega-Larson
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 3154 MRB III, PMB 407935, 465 21(st) Avenue South, Nashville, TN 37240-7935, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Shifrin
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 3154 MRB III, PMB 407935, 465 21(st) Avenue South, Nashville, TN 37240-7935, USA. Electronic address: matthew.tyska@vanderbilt.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Tyska
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008871:Microvilli / Q000378:metabolism*
chemical_list: C499675:ANKS4B protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C118970:USH1C protein, human
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